Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
May-2021 Volume 21 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2021 Volume 21 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Antiaging gene Klotho regulates epithelial‑mesenchymal transition and increases sensitivity to pemetrexed by inducing lipocalin‑2 expression

  • Authors:
    • Kyoshiro Takegahara
    • Jitsuo Usuda
    • Tatsuya Inoue
    • Takumi Sonokawa
    • Takuma Matsui
    • Mitsuo Matsumoto
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, Nippon Medical School, Tokyo 113‑8603, Japan
    Copyright: © Takegahara et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 418
    |
    Published online on: March 28, 2021
       https://doi.org/10.3892/ol.2021.12679
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Epithelial‑mesenchymal transition (EMT) is considered to serve an important role in the metastatic/invasive ability of cancer cells, in the acquisition of drug resistance, and in metabolic reprogramming. In the present study, it was hypothesized that the Klotho gene is involved in the metastatic/invasive ability of lung cancer. We previously reported an association between Klotho expression and overall survival in patients with small cell lung cancer and large cell neuroendocrine cancer. We also found that Klotho expression was associated with EMT‑related molecules in lung squamous cell carcinoma. The present study aimed to analyze the function of the Klotho gene and to elucidate its relevance to the regulation of the EMT. For this purpose, GFP‑Klotho plasmids were transfected into lung adenocarcinoma cells (A549) and cell lines with stable expression (A549/KL‑1 and A549/KL‑2) were established. A549/KL‑1 cells expressed higher levels of Klotho protein by western blot analysis compared with A549/KL‑2 cells. In western blotting of A549 and A549/KL‑1 cells, the expression of the mesenchymal marker N‑cadherin was found to be completely inhibited in A549/KL‑1 cells suggesting that Klotho expression may regulate the EMT in cancer cells via the inhibition of N‑cadherin. The results of the sensitivity tests demonstrated that A549/KL‑1 cells were significantly more sensitive to pemetrexed compared with A549 cells (IC50 A549/KL‑1 vs. A549 cells, 0.1 µM vs. 0.7 µM). The results of the microarray analysis demonstrated that a very high level of lipocalin‑2 (LCN2) expression was induced in the A549/KL‑1 cells. Klotho overexpression completely suppressed the expression of mesenchymal markers, such as N‑cadherin and Snail1 (Snail). The results of the present study suggested that there may be a new mechanism of action for the antitumor effects of pemetrexed, namely, LCN2‑mediated modulation of N‑cadherin expression. Klotho expression during cancer treatment has great potential as a predictor for efficacy of pemetrexed and as a factor in the selection of personalized medicine for postoperative adjuvant chemotherapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Henley SJ, Thomas CC, Lewis DR, Ward EM, Islami F, Wu M, Weir HK, Scott S, Sherman RL, Ma J, et al: Annual report to the nation on the status of cancer, part II: Progress toward Healthy People 2020 objectives for 4 common cancers. Cancer. 126:2250–2266. 2020. View Article : Google Scholar : PubMed/NCBI

2 

Bodor JN, Kasireddy V and Borghaei H: First-line therapies for metastatic lung adenocarcinoma without a driver mutation. J Oncol Pract. 14:529–535. 2018. View Article : Google Scholar : PubMed/NCBI

3 

Malhotra J, Jabbour SK and Aisner J: Current state of immunotherapy for non-small cell lung cancer. Transl Lung Cancer Res. 6:196–211. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Voong KR, Feliciano J, Becker D and Levy B: Beyond PD-L1 testing-emerging biomarkers for immunotherapy in non-small cell lung cancer. Ann Transl Med. 5:3762017. View Article : Google Scholar : PubMed/NCBI

5 

Chen T, You Y, Jiang H and Wang ZZ: Epithelial-mesenchymal transition (EMT): A biological process in the development, stem cell differentiation, and tumorigenesis. J Cell Physiol. 232:3261–3272. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Gravdal K, Halvorsen OJ, Haukaas SA and Akslen LA: A switch from E-cadherin to N-cadherin expression indicates epithelial to mesenchymal transition and is of strong and independent importance for the progress of prostate cancer. Clin Cancer Res. 13:7003–7011. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Kahlert C, Lahes S, Radhakrishnan P, Dutta S, Mogler C, Herpel E, Brand K, Steinert G, Schneider M, Mollenhauer M, et al: Overexpression of ZEB2 at the invasion front of colorectal cancer is an independent prognostic marker and regulates tumor invasion in vitro. Clin Cancer Res. 17:7654–7663. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Chen Q, Yang W, Wang X, Li X, Qi S, Zhang Y and Gao MQ: TGF-β1 Induces EMT in bovine mammary epithelial cells through the TGFβ1/smad signaling pathway. Cell Physiol Biochem. 43:82–93. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Jager T, Becker M, Eisenhardt A, Tilki D, Tötsch M, Schmid KW, Romics I, Rübben H, Ergün S and Szarvas T: The prognostic value of cadherin switch in bladder cancer. Oncol Rep. 23:1125–1132. 2010.PubMed/NCBI

10 

Fischer KR, Durrans A, Lee S, Sheng J, Li F, Wong ST, Choi H, El Rayes T, Ryu S, Troeger J, et al: Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature. 527:472–476. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Ryu HS, Park DJ, Kim HH, Kim WH and Lee HS: Combination of epithelial-mesenchymal transition and cancer stem cell-like phenotypes has independent prognostic value in gastric cancer. Hum Pathol. 43:520–528. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Ye X, Brabletz T, Kang Y, Longmore GD, Nieto MA, Stanger BZ, Yang J and Weinberg RA: Upholding a role for EMT in breast cancer metastasis. Nature. 547:E1–E3. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Ye X, Tam WL, Shibue T, Kaygusuz Y, Reinhardt F, Ng Eaton E and Weinberg RA: Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature. 525:256–260. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Nieto MA, Huang RY, Jackson RA and Thiery JP: EMT: 2016. Cell. 166:21–45. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Terry S, Buart S, Tan TZ, Gros G, Noman MZ, Lorens JB, Mami-Chouaib F, Thiery JP and Chouaib S: Acquisition of tumor cell phenotypic diversity along the EMT spectrum under hypoxic pressure: Consequences on susceptibility to cell-mediated cytotoxicity. Oncoimmunology. 6:e12718582017. View Article : Google Scholar : PubMed/NCBI

16 

Xu X, Zhang L, He X, Zhang P, Sun C, Xu X, Lu Y and Li F: TGF-β plays a vital role in triple-negative breast cancer (TNBC) drug-resistance through regulating stemness, EMT and apoptosis. Biochem Biophys Res Commun. 502:160–165. 2018. View Article : Google Scholar : PubMed/NCBI

17 

Tan TZ, Miow QH, Miki Y, Noda T, Mori S, Huang RY and Thiery JP: Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients. EMBO Mol Med. 6:1279–1293. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Shah PP, Dupre TV, Siskind LJ and Beverly LJ: Common cytotoxic chemotherapeutics induce epithelial-mesenchymal transition (EMT) downstream of ER stress. Oncotarget. 8:22625–22639. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, et al: Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 390:45–51. 1997. View Article : Google Scholar : PubMed/NCBI

20 

Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M and Nabeshima Y: Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun. 242:626–630. 1998. View Article : Google Scholar : PubMed/NCBI

21 

Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, et al: Suppression of aging in mice by the hormone Klotho. Science. 309:1829–1833. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Rubinek T and Wolf I: The role of alpha-klotho as a universal tumor suppressor. Vitam Horm. 101:197–214. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Delcroix V, Mauduit O, Tessier N, Montillaud A, Lesluyes T, Ducret T, Chibon F, Van Coppenolle F, Ducreux S and Vacher P: The role of the anti-aging protein klotho in IGF-1 signaling and reticular calcium leak: Impact on the chemosensitivity of dedifferentiated liposarcomas. Cancers (Basel). 10:4392018. View Article : Google Scholar

24 

Wolf I, Levanon-Cohen S, Bose S, Ligumsky H, Sredni B, Kanety H, Kuro-o M, Karlan B, Kaufman B, Koeffler HP and Rubinek T: Klotho: A tumor suppressor and a modulator of the IGF-1 and FGF pathways in human breast cancer. Oncogene. 27:7094–7105. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Xie B, Chen J, Liu B and Zhan J: Klotho acts as a tumor suppressor in cancers. Pathol Oncol Res. 19:611–617. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Wolf I, Laitman Y, Rubinek T, Abramovitz L, Novikov I, Beeri R, Kuro-O M, Koeffler HP, Catane R, Freedman LS, et al: Functional variant of KLOTHO: A breast cancer risk modifier among BRCA1 mutation carriers of Ashkenazi origin. Oncogene. 29:26–33. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Zhang J, Cao K, Pastor JV, Li L, Moe OW and Hsia CCW: Alpha-Klotho, a critical protein for lung health, is not expressed in normal lung. FASEB Bioadv. 1:675–687. 2019. View Article : Google Scholar : PubMed/NCBI

28 

Usuda J, Ichinose S, Ishizumi T, Ohtani K, Inoue T, Saji H, Kakihana M, Kajiwara N, Uchida O, Nomura M, et al: Klotho predicts good clinical outcome in patients with limited-disease small cell lung cancer who received surgery. Lung Cancer. 74:332–337. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Usuda J, Ichinose S, Ishizumi T, Ohtani K, Inoue T, Saji H, Kakihana M, Kajiwara N, Uchida O, Nomura M, et al: Klotho is a novel biomarker for good survival in resected large cell neuroendocrine carcinoma of the lung. Lung Cancer. 72:355–359. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Ibi T, Usuda J, Inoue T, Sato A and Takegahara K: Klotho expression is correlated to molecules associated with epithelial-mesenchymal transition in lung squamous cell carcinoma. Oncol Lett. 14:5526–5532. 2017.PubMed/NCBI

31 

Rollins KD and Lindley C: Pemetrexed: A multitargeted antifolate. Clin Ther. 27:1343–1382. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Liang SQ, Marti TM, Dorn P, Froment L, Hall SR, Berezowska S, Kocher G, Schmid RA and Peng RW: Blocking the epithelial-to-mesenchymal transition pathway abrogates resistance to anti-folate chemotherapy in lung cancer. Cell Death Dis. 195:e18242015. View Article : Google Scholar

33 

Buckley AF and Kakar S: Comparison of the Dako EGFR pharmDx kit and Zymed EGFR antibody for assessment of EGFR status in colorectal adenocarcinoma. Appl Immunohistochem Mol Morphol. 15:305–309. 2007. View Article : Google Scholar : PubMed/NCBI

34 

Usuda J, Azizuddin K, Chiu SM and Oleinick NL: Association between the photodynamic loss of Bcl-2 and the sensitivity to apoptosis caused by phthalocyanine photodynamic therapy. Photochem Photobiol. 78:1–8. 2003. View Article : Google Scholar : PubMed/NCBI

35 

Maehara S, Usuda J, Ishizumi T, Ichinose S, Ohtani K, Inoue T, Imai K, Furumoto H, Kudo Y, Kajiwara N, et al: Combination effect of photodynamic therapy using NPe6 with pemetrexed for human malignant pleural mesothelioma cells. Int J Oncol. 46:741–749. 2015. View Article : Google Scholar : PubMed/NCBI

36 

Booth L, Roberts JL, Tavallai M, Chuckalovcak J, Stringer DK, Koromilas AE, Boone DL, McGuire WP, Poklepovic A and Dent P: [Pemetrexed + Sorafenib] lethality is increased by inhibition of ERBB1/2/3-PI3K-NFκB compensatory survival signaling. Oncotarget. 7:23608–23632. 2016. View Article : Google Scholar : PubMed/NCBI

37 

Takahashi A, Seike M, Chiba M, Takahashi S, Nakamichi S, Matsumoto M, Takeuchi S, Minegishi Y, Noro R, Kunugi S, et al: Ankyrin repeat domain 1 overexpression is associated with common resistance to afatinib and osimertinib in EGFR-mutant lung cancer. Sci Rep. 8:148962018. View Article : Google Scholar : PubMed/NCBI

38 

Nakamichi S, Seike M, Miyanaga A, Chiba M, Zou F, Takahashi A, Ishikawa A, Kunugi S, Noro R, Kubota K and Gemma A: Overcoming drug-tolerant cancer cell subpopulations showing AXL activation and epithelial-mesenchymal transition is critical in conquering ALK-positive lung cancer. Oncotarget. 9:27242–27255. 2018. View Article : Google Scholar : PubMed/NCBI

39 

Noro R, Miyanaga A, Minegishi Y, Okano T, Seike M, Soeno C, Kataoka K, Matsuda K, Yoshimura A and Gemma A: Histone deacetylase inhibitor enhances sensitivity of non-small-cell lung cancer cells to 5-FU/S-1 via down-regulation of thymidylate synthase expression and up-regulation of p21waf1/cip1 expression. Cancer Sci. 101:1424–1430. 2010. View Article : Google Scholar : PubMed/NCBI

40 

Herbst RS, Morgensztern D and Boshoff C: The biology and management of non-small cell lung cancer. Nature. 553:446–454. 2018. View Article : Google Scholar : PubMed/NCBI

41 

Giovannetti E, Lemos C, Tekle C, Smid K, Nannizzi S, Rodriguez JA, Ricciardi S, Danesi R, Giaccone G and Peters GJ: Molecular mechanisms underlying the synergistic interaction of erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, with the multitargeted antifolate pemetrexed in non-small-cell lung cancer cells. Mol Pharmacol. 73:1290–1300. 2008. View Article : Google Scholar : PubMed/NCBI

42 

Folwaczny M, Karnesi E, Berger T and Paschos E: Clinical association between chronic periodontitis and the leukocyte extravasation inhibitors developmental endothelial locus-1 and pentraxin-3. Eur J Oral Sci. 125:258–264. 2017. View Article : Google Scholar : PubMed/NCBI

43 

Kamal Y, Schmit SL, Hoehn HJ, Amos CI and Frost HR: Transcriptomic differences between primary colorectal adenocarcinomas and distant metastases reveal metastatic colorectal cancer subtypes. Cancer Res. 79:4227–4241. 2019. View Article : Google Scholar : PubMed/NCBI

44 

Fernandez-Garcia CE, Roldan-Montero R, Tarin C, Martinez-Lopez D, Pastor-Vargas C, Blanco-Colio LM and Martín-Ventura JL: Lipocalin-2, a potential therapeutic target in advanced atherosclerosis. Atherosclerosis. 278:321–322. 2018. View Article : Google Scholar : PubMed/NCBI

45 

Doi S, Zou Y, Togao O, Pastor JV, John GB, Wang L, Shiizaki K, Gotschall R, Schiavi S, Yorioka N, et al: Klotho inhibits transforming growth factor-beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice. J Biol Chem. 286:8655–8665. 2011. View Article : Google Scholar : PubMed/NCBI

46 

Marques da Fonseca L, Jacques da Silva LR, Santos Dos Reis J, Rodrigues da Costa Santos MA, de Sousa Chaves V, Monteiro da Costa K, Sa-Diniz JN, Freire de Lima CG, Morrot A, Nunes Franklim T, et al: Piperine inhibits TGF-β signaling pathways and disrupts EMT-related events in human lung adenocarcinoma cells. Medicines (Basel). 7:192020. View Article : Google Scholar

47 

Chen B, Ma X, Liu S, Zhao W and Wu J: Inhibition of lung cancer cells growth, motility and induction of apoptosis by Klotho, a novel secreted Wnt antagonist, in a dose-dependent manner. Cancer Biol Ther. 13:1221–1228. 2012. View Article : Google Scholar : PubMed/NCBI

48 

Xu D, Yuan H, Meng Z, Yang C, Li Z, Li M, Zhang Z, Gan Y and Tu H: Cadherin 13 inhibits pancreatic cancer progression and epithelial-mesenchymal transition by Wnt/β-catenin signaling. J Cancer. 11:2101–2112. 2020. View Article : Google Scholar : PubMed/NCBI

49 

Wu MF, Hsiao YM, Huang CF, Huang YH, Yang WJ, Chan HW, Chang JT and Ko JL: Genetic determinants of pemetrexed responsiveness and nonresponsiveness in non-small cell lung cancer cells. J Thorac Oncol. 5:1143–1151. 2010. View Article : Google Scholar : PubMed/NCBI

50 

Wang YP, Yu GR, Lee MJ, Lee SY, Chu IS, Leem SH and Kim DG: Lipocalin-2 negatively modulates the epithelial-to-mesenchymal transition in hepatocellular carcinoma through the epidermal growth factor (TGF-beta1)/Lcn2/Twist1 pathway. Hepatology. 58:1349–1361. 2013. View Article : Google Scholar : PubMed/NCBI

51 

Feng M, Feng J, Chen W, Wang W, Wu X, Zhang J, Xu F and Lai M: Lipocalin2 suppresses metastasis of colorectal cancer by attenuating NF-κB-dependent activation of snail and epithelial mesenchymal transition. Mol Cancer. 15:772016. View Article : Google Scholar : PubMed/NCBI

52 

Cheng J, Chen J, Zhao Y, Yang J, Xue K and Wang Z: MicroRNA-761 suppresses remodeling of nasal mucosa and epithelial-mesenchymal transition in mice with chronic rhinosinusitis through LCN2. Stem Cell Res Ther. 11:1512020. View Article : Google Scholar : PubMed/NCBI

53 

Tao L, Shu-Ling W, Jing-Bo H, Ying Z, Rong H, Xiang-Qun L, Wen-Jie C and Lin-Fu Z: MiR-451a attenuates doxorubicin resistance in lung cancer via suppressing epithelialmesenchymal transition (EMT) through targeting c-Myc. Biomed Pharmacother. 125:1099622020. View Article : Google Scholar : PubMed/NCBI

54 

Ren D, Wang M, Guo W, Zhao X, Tu X, Huang S, Zou X and Peng X: Wild-type p53 suppresses the epithelial-mesenchymal transition and stemness in PC-3 prostate cancer cells by modulating miR145. Int J Oncol. 42:1473–1481. 2013. View Article : Google Scholar : PubMed/NCBI

55 

Kuo WT, Tu DG, Chiu LY, Sheu GT and Wu MF: High pemetrexed sensitivity of docetaxel-resistant A549 cells is mediated by TP53 status and downregulated thymidylate synthase. Oncol Rep. 38:2787–2795. 2017. View Article : Google Scholar : PubMed/NCBI

56 

Chiu LY, Hsin IL, Yang TY, Sung WW, Chi JY, Chang JT, Ko JL and Sheu GT: The ERK-ZEB1 pathway mediates epithelial-mesenchymal transition in pemetrexed resistant lung cancer cells with suppression by vinca alkaloids. Oncogene. 36:242–253. 2017. View Article : Google Scholar : PubMed/NCBI

57 

Yoon JY, Park CK, Choi YD, Oh IJ and Kim YC: Predictive factors for long-term responders of pemetrexed maintenance treatment in non-small cell lung cancer. Thorac Cancer. 10:942–949. 2019. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Takegahara K, Usuda J, Inoue T, Sonokawa T, Matsui T and Matsumoto M: Antiaging gene Klotho regulates epithelial‑mesenchymal transition and increases sensitivity to pemetrexed by inducing lipocalin‑2 expression. Oncol Lett 21: 418, 2021.
APA
Takegahara, K., Usuda, J., Inoue, T., Sonokawa, T., Matsui, T., & Matsumoto, M. (2021). Antiaging gene Klotho regulates epithelial‑mesenchymal transition and increases sensitivity to pemetrexed by inducing lipocalin‑2 expression. Oncology Letters, 21, 418. https://doi.org/10.3892/ol.2021.12679
MLA
Takegahara, K., Usuda, J., Inoue, T., Sonokawa, T., Matsui, T., Matsumoto, M."Antiaging gene Klotho regulates epithelial‑mesenchymal transition and increases sensitivity to pemetrexed by inducing lipocalin‑2 expression". Oncology Letters 21.5 (2021): 418.
Chicago
Takegahara, K., Usuda, J., Inoue, T., Sonokawa, T., Matsui, T., Matsumoto, M."Antiaging gene Klotho regulates epithelial‑mesenchymal transition and increases sensitivity to pemetrexed by inducing lipocalin‑2 expression". Oncology Letters 21, no. 5 (2021): 418. https://doi.org/10.3892/ol.2021.12679
Copy and paste a formatted citation
x
Spandidos Publications style
Takegahara K, Usuda J, Inoue T, Sonokawa T, Matsui T and Matsumoto M: Antiaging gene Klotho regulates epithelial‑mesenchymal transition and increases sensitivity to pemetrexed by inducing lipocalin‑2 expression. Oncol Lett 21: 418, 2021.
APA
Takegahara, K., Usuda, J., Inoue, T., Sonokawa, T., Matsui, T., & Matsumoto, M. (2021). Antiaging gene Klotho regulates epithelial‑mesenchymal transition and increases sensitivity to pemetrexed by inducing lipocalin‑2 expression. Oncology Letters, 21, 418. https://doi.org/10.3892/ol.2021.12679
MLA
Takegahara, K., Usuda, J., Inoue, T., Sonokawa, T., Matsui, T., Matsumoto, M."Antiaging gene Klotho regulates epithelial‑mesenchymal transition and increases sensitivity to pemetrexed by inducing lipocalin‑2 expression". Oncology Letters 21.5 (2021): 418.
Chicago
Takegahara, K., Usuda, J., Inoue, T., Sonokawa, T., Matsui, T., Matsumoto, M."Antiaging gene Klotho regulates epithelial‑mesenchymal transition and increases sensitivity to pemetrexed by inducing lipocalin‑2 expression". Oncology Letters 21, no. 5 (2021): 418. https://doi.org/10.3892/ol.2021.12679
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team