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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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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.

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

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

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

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

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

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

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Article

HIF-1α activation under glucose deprivation plays a central role in the acquisition of anti-apoptosis in human colon cancer cells

  • Authors:
    • Arata Nishimoto
    • Naruji Kugimiya
    • Tohru Hosoyama
    • Tadahiko Enoki
    • Tao-Sheng Li
    • Kimikazu Hamano
  • View Affiliations / Copyright

    Affiliations: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan, Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan
  • Pages: 2077-2084
    |
    Published online on: April 3, 2014
       https://doi.org/10.3892/ijo.2014.2367
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Abstract

A poor vascular network development in a tumor mass leads to poor oxygen and nutrient supply. To adapt to a hypoxic microenvironment, it is well-known that cancer cells activate the transcription factor hypoxia-inducible factor-1α (HIF-1α). HIF-1α plays a central role in hypoxia-induced metabolic switching, anti-apoptosis, angiogenesis and drug resistance. Glucose deprivation, another major stressful microenvironment, protects cancer cells from drug-induced apoptosis. However, the molecular mechanisms by which cancer cells adapt to poor nutrient conditions remain poorly understood. In this study, we focused on HIF-1α, signal transducer and activator of transcription 3 (STAT3) and trans­cription factor 4 (TCF4), which are involved in cell survival, anti-apoptosis and drug resistance. We examined their activities and the relationships among these transcription factors under glucose deprivation. Our results showed that glucose deprivation increased HIF-1α, STAT3 and TCF4 DNA-binding activity, as well as the expression levels of their target genes OCT4, BCL-2 and VEGF. HIF-1α knockdown significantly increased poly(ADP-ribose) polymerase 1 (PARP-1) cleavage at higher levels than STAT3 knockdown under glucose deprivation. Furthermore, HIF-1α knockdown led to a significant decrease in the expression levels of both STAT3 and TCF4, although STAT3 knockdown decreased only HIF-1α expression level. Our data indicated that activation of the HIF-1α signaling pathway under glucose deprivation leads to the acquisition of anti-apoptotic properties in human colon cancer cells, and targeting the HIF-1α signaling pathway may provide an effective avenue for treating cancers resistant to conventional therapy.
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1. 

Warburg O: On the origin of cancer cells. Science. 123:309–314. 1956. View Article : Google Scholar : PubMed/NCBI

2. 

Hirayama A, Kami K, Sugimoto M, et al: Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. Cancer Res. 69:4918–4925. 2009. View Article : Google Scholar : PubMed/NCBI

3. 

Zhou J, Schmid T, Schnitzer S and Brüne B: Tumor hypoxia and cancer progression. Cancer Lett. 237:10–21. 2006. View Article : Google Scholar

4. 

Cummins EP and Taylor CT: Hypoxia-responsive transcription factors. Eur J Physiol. 450:363–371. 2005. View Article : Google Scholar : PubMed/NCBI

5. 

Selvendiran K, Bratasz A, Kuppusamy ML, et al: Hypoxia induces chemoresistance in ovarian cancer cells by activation of signal transducer and activator of transcription 3. Int J Cancer. 125:2198–2204. 2009. View Article : Google Scholar : PubMed/NCBI

6. 

Oh M-K, Park H-J, Kim N-H, et al: Hypoxia-inducible factor-1α enhances haptoglobin gene expression by improving binding of STAT3 to the promoter. J Biol Chem. 286:8857–8865. 2011.

7. 

Ledoux S, Yang R, Friedlander G and Laouari D: Glucose depletion enhances P-glycoprotein expression in hepatoma cells: role of endoplasmic reticulum stress response. Cancer Res. 63:7284–7290. 2003.PubMed/NCBI

8. 

Cui H, Darmanin S, Natsuisaka M, et al: Enhanced expression of asparagine synthetase under glucose-deprived conditions protects pancreatic cancer cells from apoptosis induced by glucose deprivation and cisplatin. Cancer Res. 67:3345–3355. 2007. View Article : Google Scholar

9. 

Duan Z, Foster R, Bell DA, et al: Signal transducer and activator of transcription 3 pathway activation in drug-resistant ovarian cancer. Clin Cancer Res. 12:5055–5063. 2006. View Article : Google Scholar : PubMed/NCBI

10. 

Liu L, Ning X, Sun L, et al: Hypoxia-inducible factor-1α contributes to hypoxia-induced chemoresistance in gastric cancer. Cancer Sci. 99:121–128. 2008.

11. 

Kendziorra E, Ahlborn K, Spitzner M, et al: Silencing of the Wnt transcription factor TCF4 sensitizes colorectal cancer cells to (chemo-) radiotherapy. Carcinogenesis. 32:1824–1831. 2011. View Article : Google Scholar : PubMed/NCBI

12. 

Lee AS: GRP78 induction in cancer: therapeutic and prognostic implications. Cancer Res. 67:3496–3499. 2007. View Article : Google Scholar : PubMed/NCBI

13. 

Mathieu J, Zhang Z, Zhou W, et al: HIF induces human embryonic stem cell markers in cancer cells. Cancer Res. 71:4640–4652. 2011. View Article : Google Scholar

14. 

Real PJ, Sierra A, Juan A, et al: Resistance to chemotherapy via Stat3-dependent overexpression of Bcl-2 in metastatic breast cancer cells. Oncogene. 21:7611–7618. 2002. View Article : Google Scholar : PubMed/NCBI

15. 

Forsythe JA, Jiang BH, Iyer NV, et al: Activation of vascular endothelial growth factor gene transcription by hypoxiainducible factor 1. Mol Cell Biol. 16:4604–4613. 1996.PubMed/NCBI

16. 

Niu G, Wright KL, Huang M, et al: Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene. 21:2000–2008. 2002. View Article : Google Scholar

17. 

Hwang I, Kim J and Jeing S: β-catenin and peroxisome proliferator-activated receptor-δ coordinate dynamic chromatin loops for the transcription of vascular endothelial growth factor A gene in colon cancer cells. J Biol Chem. 287:41364–41373. 2012.

18. 

Rodda DJ, Chew J-L, Lim L-H, et al: Transcriptional regulation of Nanog by OCT4 and SOX2. J Biol Chem. 280:24731–24737. 2005. View Article : Google Scholar : PubMed/NCBI

19. 

Izuishi K, Kato K, Ogura T, et al: Remarkable tolerance of tumor cells to nutrient deprivation: possible new biochemical target for cancer therapy. Cancer Res. 60:6201–6207. 2000.

20. 

Korinek V, Barker N, Morin PJ, et al: Constitutive transcriptional activation by a β-catenin-Tcf complex in APC−/− colon carcinoma. Science. 275:1784–1787. 1997.

21. 

Reed JC: Regulation of apoptosis by bcl-2 family proteins and its role in cancer and chemoresistance. Curr Opin Oncol. 7:541–546. 1995. View Article : Google Scholar : PubMed/NCBI

22. 

Samuel S, Fan F, Dang LH, et al: Intracrine vascular endothelial growth factor signaling in survival and chemoresistance of human colorectal cancer cells. Oncogene. 30:1205–1212. 2011. View Article : Google Scholar : PubMed/NCBI

23. 

Loh Y-H, Ng J-H and Ng H-H: Molecular framework underlying pluripotency. Cell Cycle. 7:885–891. 2008. View Article : Google Scholar : PubMed/NCBI

24. 

Chiou S, Wang M-L, Chou Y-T, et al: Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res. 70:10433–10444. 2010. View Article : Google Scholar : PubMed/NCBI

25. 

Vaiopoulos AG, Kostakis ID, Koutsilieris M and Papavassiliou AG: Concise review: colorectal cancer stem cells. Stem Cells. 30:363–371. 2012. View Article : Google Scholar

26. 

Kim J-W and Dang CV: Cancer’s molecular sweet tooth and the Warburg effect. Cancer Res. 66:8927–8930. 2006.

27. 

Kaelin WG Jr and Thompson CB: Clues from cell metabolism. Nature. 465:562–564. 2010. View Article : Google Scholar : PubMed/NCBI

28. 

Liu X-W, Su Y, Zhu H, et al: HIF-1α-dependent autophagy protects Hela cells from fenretinide (4-HPR)-induced apoptosis in hypoxia. Pharmacol Res. 62:416–425. 2010.

29. 

Jung JE, Lee H-G, Cho I-H, et al: STAT3 is a potential modulator of HIF-1-mediated VEGF expression in human renal carcinoma cells. FASEB J. 19:1296–1298. 2005.PubMed/NCBI

30. 

Xu Q, Briggs J, Park S, et al: Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways. Oncogene. 24:5552–5560. 2005. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Nishimoto A, Kugimiya N, Hosoyama T, Enoki T, Li T and Hamano K: HIF-1α activation under glucose deprivation plays a central role in the acquisition of anti-apoptosis in human colon cancer cells. Int J Oncol 44: 2077-2084, 2014.
APA
Nishimoto, A., Kugimiya, N., Hosoyama, T., Enoki, T., Li, T., & Hamano, K. (2014). HIF-1α activation under glucose deprivation plays a central role in the acquisition of anti-apoptosis in human colon cancer cells. International Journal of Oncology, 44, 2077-2084. https://doi.org/10.3892/ijo.2014.2367
MLA
Nishimoto, A., Kugimiya, N., Hosoyama, T., Enoki, T., Li, T., Hamano, K."HIF-1α activation under glucose deprivation plays a central role in the acquisition of anti-apoptosis in human colon cancer cells". International Journal of Oncology 44.6 (2014): 2077-2084.
Chicago
Nishimoto, A., Kugimiya, N., Hosoyama, T., Enoki, T., Li, T., Hamano, K."HIF-1α activation under glucose deprivation plays a central role in the acquisition of anti-apoptosis in human colon cancer cells". International Journal of Oncology 44, no. 6 (2014): 2077-2084. https://doi.org/10.3892/ijo.2014.2367
Copy and paste a formatted citation
x
Spandidos Publications style
Nishimoto A, Kugimiya N, Hosoyama T, Enoki T, Li T and Hamano K: HIF-1α activation under glucose deprivation plays a central role in the acquisition of anti-apoptosis in human colon cancer cells. Int J Oncol 44: 2077-2084, 2014.
APA
Nishimoto, A., Kugimiya, N., Hosoyama, T., Enoki, T., Li, T., & Hamano, K. (2014). HIF-1α activation under glucose deprivation plays a central role in the acquisition of anti-apoptosis in human colon cancer cells. International Journal of Oncology, 44, 2077-2084. https://doi.org/10.3892/ijo.2014.2367
MLA
Nishimoto, A., Kugimiya, N., Hosoyama, T., Enoki, T., Li, T., Hamano, K."HIF-1α activation under glucose deprivation plays a central role in the acquisition of anti-apoptosis in human colon cancer cells". International Journal of Oncology 44.6 (2014): 2077-2084.
Chicago
Nishimoto, A., Kugimiya, N., Hosoyama, T., Enoki, T., Li, T., Hamano, K."HIF-1α activation under glucose deprivation plays a central role in the acquisition of anti-apoptosis in human colon cancer cells". International Journal of Oncology 44, no. 6 (2014): 2077-2084. https://doi.org/10.3892/ijo.2014.2367
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