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 Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
April-2017 Volume 37 Issue 4

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
April-2017 Volume 37 Issue 4

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

High expression of PINK1 promotes proliferation and chemoresistance of NSCLC

  • Authors:
    • Rui Zhang
    • Jun Gu
    • Jie Chen
    • Jun Ni
    • Jieru Hung
    • Zhiwen Wang
    • Xiaochen Zhang
    • Jian Feng
    • Lili Ji
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Disease, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Rehabilitation, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226200, P.R. China, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Intensive Care Unit, Qidong People's Hospital, Nantong, Jiangsu 226200, P.R. China, Department of Pathology, Medical College of Nantong University, Nantong, Jiangsu 226001, P.R. China
  • Pages: 2137-2146
    |
    Published online on: March 2, 2017
       https://doi.org/10.3892/or.2017.5486
  • 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

PTEN-induced putative kinase 1 (PINK1) was identified initially as a gene upregulated in cancer cells which regulates cellular processes of significance in cancer cell biology, including cell survival, stress resistance and the cell cycle. However, the expression and function of PINK1 in non-small cell lung cancer (NSCLC) has not been determined yet. We demonstrated high PINK1 expression in NSCLC tumor tissues and cell lines as assessed by western blot and immunohistochemistry (IHC) assays. In addition, IHC analysis revealed that PINK1 expression was associated with a more invasive tumor phenotype and poor prognosis. Furthermore, in vitro studies using upregulation and knockdown of PINK1 confirmed that PINK1 promoted cell proliferation of NSCLC, which might be through as the NF-κB pathway. Moreover, we also demonstrated that downregulation of PINK1 enhanced cisplatin (CDDP)-induced NSCLC cell apoptosis. Together, our findings indicate that PINK1 plays a significant role in NSCLC progression and chemoresistance, and highlights its potential role as a target in future anticancer therapies.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, et al: SEER Cancer Statistics Review. 1975–2012. National Cancer Institute; 2015 http://seer.cancer.gov/csr/1975_2012/Accessed. November 18–2015

3 

Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J and Johnson DH: Eastern Cooperative Oncology Group: Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 346:92–98. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Unoki M and Nakamura Y: Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway. Oncogene. 20:4457–4465. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, et al: Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science. 304:1158–1160. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Mills RD, Sim CH, Mok SS, Mulhern TD, Culvenor JG and Cheng HC: Biochemical aspects of the neuroprotective mechanism of PTEN-induced kinase-1 (PINK1). J Neurochem. 105:18–33. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Arena G, Gelmetti V, Torosantucci L, Vignone D, Lamorte G, De Rosa P, Cilia E, Jonas EA and Valente EM: PINK1 protects against cell death induced by mitochondrial depolarization, by phosphorylating Bcl-xL and impairing its pro-apoptotic cleavage. Cell Death Differ. 20:920–930. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Pridgeon JW, Olzmann JA, Chin LS and Li L: PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1. PLoS Biol. 5:e1722007. View Article : Google Scholar : PubMed/NCBI

9 

Wood-Kaczmar A, Gandhi S, Yao Z, Abramov AY, Miljan EA, Keen G, Stanyer L, Hargreaves I, Klupsch K, Deas E, et al: PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons. PLoS One. 3:e24552008. View Article : Google Scholar : PubMed/NCBI

10 

Klinkenberg M, Thurow N, Gispert S, Ricciardi F, Eich F, Prehn JH, Auburger G and Kögel D: Enhanced vulnerability of PARK6 patient skin fibroblasts to apoptosis induced by proteasomal stress. Neuroscience. 166:422–434. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Wu Z, Sawada T, Shiba K, Liu S, Kanao T, Takahashi R, Hattori N, Imai Y and Lu B: Tricornered/NDR kinase signaling mediates PINK1-directed mitochondrial quality control and tissue maintenance. Genes Dev. 27:157–162. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Lee HJ and Chung KC: PINK1 positively regulates IL-1β-mediated signaling through Tollip and IRAK1 modulation. J Neuroinflammation. 9:2712012. View Article : Google Scholar : PubMed/NCBI

13 

Akundi RS, Huang Z, Eason J, Pandya JD, Zhi L, Cass WA, Sullivan PG and Büeler H: Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice. PLoS One. 6:e160382011. View Article : Google Scholar : PubMed/NCBI

14 

Berthier A, Navarro S, Jiménez-Sáinz J, Roglá I, Ripoll F, Cervera J and Pulido R: PINK1 displays tissue-specific subcellular location and regulates apoptosis and cell growth in breast cancer cells. Hum Pathol. 42:75–87. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Murata H, Sakaguchi M, Jin Y, Sakaguchi Y, Futami J, Yamada H, Kataoka K and Huh NH: A new cytosolic pathway from a Parkinson disease-associated kinase, BRPK/PINK1: Activation of AKT via mTORC2. J Biol Chem. 286:7182–7189. 2011. View Article : Google Scholar : PubMed/NCBI

16 

O'Flanagan CH, Morais VA, Wurst W, De Strooper B and O'Neill C: The Parkinson's gene PINK1 regulates cell cycle progression and promotes cancer-associated phenotypes. Oncogene. 34:1363–1374. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Akundi RS, Zhi L and Büeler H: PINK1 enhances insulin-like growth factor-1-dependent Akt signaling and protection against apoptosis. Neurobiol Dis. 45:469–478. 2012. View Article : Google Scholar : PubMed/NCBI

18 

MacKeigan JP, Murphy LO and Blenis J: Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance. Nat Cell Biol. 7:591–600. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Rathos MJ, Khanwalkar H, Joshi K, Manohar SM and Joshi KS: Potentiation of in vitro and in vivo antitumor efficacy of doxorubicin by cyclin-dependent kinase inhibitor P276-00 in human non-small cell lung cancer cells. BMC Cancer. 13:292013. View Article : Google Scholar : PubMed/NCBI

20 

Yang L, Zhou Y, Li Y, Zhou J, Wu Y, Cui Y, Yang G and Hong Y: Mutations of p53 and KRAS activate NF-κB to promote chemoresistance and tumorigenesis via dysregulation of cell cycle and suppression of apoptosis in lung cancer cells. Cancer Lett. 357:520–526. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Lee HJ, Jang SH, Kim H, Yoon JH and Chung KC: PINK1 stimulates interleukin-1β-mediated inflammatory signaling via the positive regulation of TRAF6 and TAK1. Cell Mol Life Sci. 69:3301–3315. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Ni T, Mao G, Xue Q, Liu Y, Chen B, Cui X, Lv L, Jia L, Wang Y and Ji L: Upregulated expression of ILF2 in non-small cell lung cancer is associated with tumor cell proliferation and poor prognosis. J Mol Histol. 46:325–335. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Xue Q, Zhou Y, Wan C, Lv L, Chen B, Cao X, Ju G, Huang Y, Ni R and Mao G: Epithelial membrane protein 3 is frequently shown as promoter methylation and functions as a tumor suppressor gene in non-small cell lung cancer. Exp Mol Pathol. 95:313–318. 2013. View Article : Google Scholar : PubMed/NCBI

24 

O'Flanagan CH, Morais VA and O'Neill C: PINK1, cancer and neurodegeneration. Oncoscience. 3:1–2. 2016.PubMed/NCBI

25 

O'Flanagan CH and O'Neill C: Pink1 signalling in cancer biology. Biochim Biophys Acta. 1846:590–598. 2014.PubMed/NCBI

26 

Martin SA, Hewish M, Sims D, Lord CJ and Ashworth A: Parallel high-throughput RNA interference screens identify PINK1 as a potential therapeutic target for the treatment of DNA mismatch repair-deficient cancers. Cancer Res. 71:1836–1848. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Lin W and Kang UJ: Structural determinants of PINK1 topology and dual subcellular distribution. BMC Cell Biol. 11:902010. View Article : Google Scholar : PubMed/NCBI

28 

Deng H, Jankovic J, Guo Y, Xie W and Le W: Small interfering RNA targeting the PINK1 induces apoptosis in dopaminergic cells SH-SY5Y. Biochem Biophys Res Commun. 337:1133–1138. 2005. View Article : Google Scholar : PubMed/NCBI

29 

Cui T, Fan C, Gu L, Gao H, Liu Q, Zhang T, Qi Z, Zhao C, Zhao H, Cai Q, et al: Silencing of PINK1 induces mitophagy via mitochondrial permeability transition in dopaminergic MN9D cells. Brain Res. 1394:1–13. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Lee KS, Wu Z, Song Y, Mitra SS, Feroze AH, Cheshier SH and Lu B: Roles of PINK1, mTORC2, and mitochondria in preserving brain tumor-forming stem cells in a noncanonical Notch signaling pathway. Genes Dev. 27:2642–2647. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Su JL, Cheng X, Yamaguchi H, Chang YW, Hou CF, Lee DF, Ko HW, Hua KT, Wang YN, Hsiao M, et al: Foxo3a-dependent mechanism of e1a-induced chemosensitization. Cancer Res. 71:6878–6887. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Sunters A, Madureira PA, Pomeranz KM, Aubert M, Brosens JJ, Cook SJ, Burgering BM, Coombes RC and Lam EW: Paclitaxel-induced nuclear translocation of FOXO3a in breast cancer cells is mediated by c-Jun NH2-terminal kinase and Akt. Cancer Res. 66:212–220. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang R, Gu J, Chen J, Ni J, Hung J, Wang Z, Zhang X, Feng J and Ji L: High expression of PINK1 promotes proliferation and chemoresistance of NSCLC. Oncol Rep 37: 2137-2146, 2017.
APA
Zhang, R., Gu, J., Chen, J., Ni, J., Hung, J., Wang, Z. ... Ji, L. (2017). High expression of PINK1 promotes proliferation and chemoresistance of NSCLC. Oncology Reports, 37, 2137-2146. https://doi.org/10.3892/or.2017.5486
MLA
Zhang, R., Gu, J., Chen, J., Ni, J., Hung, J., Wang, Z., Zhang, X., Feng, J., Ji, L."High expression of PINK1 promotes proliferation and chemoresistance of NSCLC". Oncology Reports 37.4 (2017): 2137-2146.
Chicago
Zhang, R., Gu, J., Chen, J., Ni, J., Hung, J., Wang, Z., Zhang, X., Feng, J., Ji, L."High expression of PINK1 promotes proliferation and chemoresistance of NSCLC". Oncology Reports 37, no. 4 (2017): 2137-2146. https://doi.org/10.3892/or.2017.5486
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang R, Gu J, Chen J, Ni J, Hung J, Wang Z, Zhang X, Feng J and Ji L: High expression of PINK1 promotes proliferation and chemoresistance of NSCLC. Oncol Rep 37: 2137-2146, 2017.
APA
Zhang, R., Gu, J., Chen, J., Ni, J., Hung, J., Wang, Z. ... Ji, L. (2017). High expression of PINK1 promotes proliferation and chemoresistance of NSCLC. Oncology Reports, 37, 2137-2146. https://doi.org/10.3892/or.2017.5486
MLA
Zhang, R., Gu, J., Chen, J., Ni, J., Hung, J., Wang, Z., Zhang, X., Feng, J., Ji, L."High expression of PINK1 promotes proliferation and chemoresistance of NSCLC". Oncology Reports 37.4 (2017): 2137-2146.
Chicago
Zhang, R., Gu, J., Chen, J., Ni, J., Hung, J., Wang, Z., Zhang, X., Feng, J., Ji, L."High expression of PINK1 promotes proliferation and chemoresistance of NSCLC". Oncology Reports 37, no. 4 (2017): 2137-2146. https://doi.org/10.3892/or.2017.5486
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