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
August-2014 Volume 32 Issue 2

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
August-2014 Volume 32 Issue 2

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

CD166 plays a pro-carcinogenic role in liver cancer cells via inhibition of FOXO proteins through AKT

  • Authors:
    • Wenjun Yu
    • Jiayi Wang
    • Lifang Ma
    • Xun Tang
    • Yongxia Qiao
    • Quihui Pan
    • Yongchun Yu
    • Fenyong Sun
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, P.R. China, School of Public Health, Shanghai Jiaotong University, Shanghai 200025, P.R. China, Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, P.R. China, Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai TCM University, Shanghai 200071, P.R. China
  • Pages: 677-683
    |
    Published online on: May 30, 2014
       https://doi.org/10.3892/or.2014.3226
  • 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

Cluster of differentiation 166 (CD166) is a cell surface membrane protein, which is regarded as a valuable prognostic marker in several types of epithelial tumors. We previously reported that CD166 exerts its pro-carcinogenic role by enhancing YAP function in liver cancer cells. However, YAP cannot completely rescue the increased anti‑carcinogenic effects by gene silencing of CD166, whose downstream effectors require further investigation. Here, we found that knockdown of CD166 inhibits phosphorylation of anti-carcinogenic FOXO proteins. Overexpression of CD166 led, not only to a faster protein degradation rate, but also a more accumulated ubiquitination of FOXO compared to the control. Moreover, overexpression of CD166 facilitated FOXO protein localization from the nuclear fraction to the cytosolic fraction, suggesting that CD166 modulates FOXO protein stability through alteration of their subcellular localization. In addition, simultaneous overexpression of CD166 partially reversed the evoked anti-carcinogenic effects by overexpression of FOXO both in vitro and in vivo. Furthermore, CD166 knockdown‑induced anti‑carcinogenic effects and dephosphorylation of FOXO proteins were rescued by overexpression of AKT. In liver cancer tissues, we also observed that higher expression levels of CD166, phospho-AKT, total AKT and phospho‑FOXO were correlated with lower expression levels of total FOXO, suggesting that the upregulation of CD166 leads to the activation of AKT, which in turn facilitates phosphorylation and degradation of FOXO. Taken together, our data demonstrate that AKT is an inter-mediator between the upstream regulator, CD166, and downstream effector, FOXO, in liver cancer cells. Disrupting the relationship between CD166 and the AKT/FOXO axis may serve as a novel therapeutic target for liver cancer patients.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

van Kempen LC, Nelissen JM, Degen WG, Torensma R, Weidle UH, Bloemers HP, Figdor CG and Swart GW: Molecular basis for the homophilic activated leukocyte cell adhesion molecule (ALCAM)-ALCAM interaction. J Biol Chem. 276:25783–25790. 2001.PubMed/NCBI

2 

Weichert W, Knösel T, Bellach J, Dietel M and Kristiansen G: ALCAM/CD166 is overexpressed in colorectal carcinoma and correlates with shortened patient survival. J Clin Pathol. 57:1160–1164. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Burkhardt M, Mayordomo E, Winzer KJ, Fritzsche F, Gansukh T, Pahl S, Weichert W, Denkert C, Guski H and Dietel MG: Cytoplasmic overexpression of ALCAM is prognostic of disease progression in breast cancer. J Clin Pathol. 59:403–409. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Kahlert C, Weber H, Mogler C, Bergmann F, Schirmacher P, Kenngott HG, Matterne U, Mollberg N, Rahbari NN, Hinz U, Koch M, Aigner M and Weitz J: Increased expression of ALCAM/CD166 in pancreatic cancer is an independent prognostic marker for poor survival and early tumour relapse. Br J Cancer. 101:457–464. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Jezierska A, Matysiak W and Motyl T: ALCAM/CD166 protects breast cancer cells against apoptosis and autophagy. Med Sci Monit. 12:BR263–BR273. 2006.PubMed/NCBI

6 

Wang J, Gu Z, Ni P, Qiao Y, Chen C, Liu X, Lin J, Chen N and Fan Q: NF-κB P50/P65 hetero-dimer mediates differential regulation of CD166/ALCAM expression via interaction with micoRNA-9 after serum deprivation, providing evidence for a novel negative auto-regulatory loop. Nucleic Acids Res. 39:6440–6455. 2011.

7 

Ma L, Wang J, Lin J, Pan Q, Yu Y and Sun F: Cluster of differentiation 166 (CD166) regulated by phosphatidylinositide 3-kinases (PI3K)/AKT signaling to exert its anti-apoptotic role via yes associated protein (YAP) in liver cancer. J Biol Chem. Jan 30–2014.(Epub ahead of print). View Article : Google Scholar

8 

Zhang X, Tang N, Hadden TJ and Rishi AK: Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta. 1813:1978–1986. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Medema RH, Kops GJ, Bos JL and Burgering BM: AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature. 404:782–787. 2000. View Article : Google Scholar : PubMed/NCBI

10 

Urbich C, Knau A, Fichtlscherer S, Walter DH, Brühl T, Potente M, Hofmann WK, de Vos S, Zeiher AM and Dimmeler S: FOXO-dependent expression of the proapoptotic protein Bim: pivotal role for apoptosis signaling in endothelial progenitor cells. FASEB J. 19:974–976. 2005.PubMed/NCBI

11 

Carbajo-Pescador S, Mauriz JL, García-Palomo A and González-Gallego J: FoxO proteins: regulation and molecular targets in liver cancer. Curr Med Chem. 21:1231–1246. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Wang J, Ma L, Weng W, Qiao Y, Zhang Y, He J, Wang H, Xiao W, Li L, Chu Q, Pan Q, Yu Y and Sun F: Mutual interaction between YAP and CREB promotes tumorigenesis in liver cancer. Hepatology. 58:1011–1020. 2013. View Article : Google Scholar : PubMed/NCBI

13 

You H, Yamamoto K and Mak TW: Regulation of transactivation-independent proapoptotic activity of p53 by FOXO3a. Proc Natl Acad Sci USA. 103:9051–9056. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Yamashita M, Ying SX, Zhang GM, Li C, Cheng SY, Deng CX and Zhang YE: Ubiquitin ligase Smurf1 controls osteoblast activity and bone homeostasis by targeting MEKK2 for degradation. Cell. 121:101–113. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Sapkota G, Alarcon C, Spagnoli FM, Brivanlou AH and Massague J: Balancing BMP signaling through integrated inputs into the Smad1 linker. Mol Cell. 25:441–454. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Fu Z and Tindall DJ: FOXOs, cancer and regulation of apoptosis. Oncogene. 27:2312–2319. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Hales EC, Taub JW and Matherly LH: New insights into Notch1 regulation of the PI3K-AKT-mTOR1 signaling axis: targeted therapy of γ-secretase inhibitor resistant T-cell acute lymphoblastic leukemia. Cell Signal. 26:149–161. 2014.PubMed/NCBI

18 

Lin A, Yao J, Zhuang L, Wang D, Han J and Lam EW; TCGA Research Network and Gan B. The FoxO-BNIP3 axis exerts a unique regulation of mTORC1 and cell survival under energy stress. Oncogene. Jul 15–2013.(Epub ahead of print). View Article : Google Scholar

19 

Tao GZ, Lehwald N, Jang KY, Baek J, Xu B, Omary MB and Sylvester KG: Wnt/β-catenin signaling protects mouse liver against oxidative stress-induced apoptosis through the inhibition of forkhead transcription factor FoxO3. J Biol Chem. 28:17214–17224. 2013.

20 

Yusuf I, Zhu X, Kharas MGs, Chen J and Fruman DA: Optimal B-cell proliferation requires phosphoinositide 3-kinase-dependent inactivation of FOXO transcription factors. Blood. 104:784–787. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Wang J, Zhang Y, Weng W, Qiao Y, Ma L, Xiao W, Yu Y, Pan Q and Sun F: Impaired phosphorylation and ubiquitination by p70 S6 kinase (p70S6K) and smad ubiquitination regulatory factor 1 (Smurf1) promote tribbles homolog 2 (TRIB2) stability and carcinogenic property in liver cancer. J Biol Chem. 288:33667–33681. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Wang J, Park JS, Wei Y, Rajurkar M, Cotton JL, Fan Q, Lewis BC, Ji H and Mao J: TRIB2 acts downstream of Wnt/TCF in liver cancer cells to regulate YAP and C/EBPα function. Mol Cell. 51:211–225. 2013.PubMed/NCBI

23 

Zanella F, Renner O, García B, Callejas S, Dopazo A, Peregrina S, Carnero A and Link W: Human TRIB2 is a repressor of FOXO that contributes to the malignant phenotype of melanoma cells. Oncogene. 29:2973–2982. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Manning BD and Cantley LC: AKT/PKB signaling: navigating downstream. Cell. 129:1261–1274. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yu W, Wang J, Ma L, Tang X, Qiao Y, Pan Q, Yu Y and Sun F: CD166 plays a pro-carcinogenic role in liver cancer cells via inhibition of FOXO proteins through AKT. Oncol Rep 32: 677-683, 2014.
APA
Yu, W., Wang, J., Ma, L., Tang, X., Qiao, Y., Pan, Q. ... Sun, F. (2014). CD166 plays a pro-carcinogenic role in liver cancer cells via inhibition of FOXO proteins through AKT. Oncology Reports, 32, 677-683. https://doi.org/10.3892/or.2014.3226
MLA
Yu, W., Wang, J., Ma, L., Tang, X., Qiao, Y., Pan, Q., Yu, Y., Sun, F."CD166 plays a pro-carcinogenic role in liver cancer cells via inhibition of FOXO proteins through AKT". Oncology Reports 32.2 (2014): 677-683.
Chicago
Yu, W., Wang, J., Ma, L., Tang, X., Qiao, Y., Pan, Q., Yu, Y., Sun, F."CD166 plays a pro-carcinogenic role in liver cancer cells via inhibition of FOXO proteins through AKT". Oncology Reports 32, no. 2 (2014): 677-683. https://doi.org/10.3892/or.2014.3226
Copy and paste a formatted citation
x
Spandidos Publications style
Yu W, Wang J, Ma L, Tang X, Qiao Y, Pan Q, Yu Y and Sun F: CD166 plays a pro-carcinogenic role in liver cancer cells via inhibition of FOXO proteins through AKT. Oncol Rep 32: 677-683, 2014.
APA
Yu, W., Wang, J., Ma, L., Tang, X., Qiao, Y., Pan, Q. ... Sun, F. (2014). CD166 plays a pro-carcinogenic role in liver cancer cells via inhibition of FOXO proteins through AKT. Oncology Reports, 32, 677-683. https://doi.org/10.3892/or.2014.3226
MLA
Yu, W., Wang, J., Ma, L., Tang, X., Qiao, Y., Pan, Q., Yu, Y., Sun, F."CD166 plays a pro-carcinogenic role in liver cancer cells via inhibition of FOXO proteins through AKT". Oncology Reports 32.2 (2014): 677-683.
Chicago
Yu, W., Wang, J., Ma, L., Tang, X., Qiao, Y., Pan, Q., Yu, Y., Sun, F."CD166 plays a pro-carcinogenic role in liver cancer cells via inhibition of FOXO proteins through AKT". Oncology Reports 32, no. 2 (2014): 677-683. https://doi.org/10.3892/or.2014.3226
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