Understanding the relationship between HIF-1 alpha, Hypoxia and Epithelial-Mesenchymal Transition

Thu, 05/12/2016 - 11:02

Epithelial-mesenchymal transition (EMT) is a natural process by which epithelial cells lose their polarity and intercellular adhesion, and gain the migratory invasive properties of mesenchymal stem cells that can differentiate into a variety of cell types. EMT is critical to many developmental processes including embryo development and wound healing. However, EMT is also a fundamental step in the initiation of metastasis during cancer progression.

Hypoxia is known to induce EMT via HIF-1 alpha induction. Researchers have used HIF-1 alpha antibodies (NB100-105), (NB100-449) and (NB100-479) to help identify the molecular mechanisms by which hypoxia promotes carcinoma invasion and metastasis. Specifically, HIF-1 alpha has been shown to orchestrate EMT and metastasis through the coordinated regulation of a variety of different EMT regulators, including TWIST (Yang et al., 2008), SNAIL (Liu et al., 2011, Zhang et al., 2013), and ZEB1 (Zhang et al., 2015).

HIF-1 alpha antibody HIF-1 alpha antibody
IHC analysis of HIF-1 alpha antibody (NB100-131) in paraffin-embedded mouse kidney.

IF analysis of HIF-1 alpha antibody (NB100-449) in HeLa cells

Vimentin has long been known to be an important mesenchymal marker of EMT. However HIF-1 alpha’s central role in the promotion of EMT induced metastasis, along with its role in angiogenesis, have led researchers to use HIF-1 alpha as a key prognostic indicator in many cancers. For example, researchers using Novus' HIF-1 alpha antibody clone ESEE122 (NB100-131) found that HIF-1 alpha expression correlates to poor survival prognosis in lung cancer (Giatromanolaki et al., 2001), oral cancer (Eckert et al., 2011), and cervical cancer (Kim et al., 2013).

Alternatively, this role also makes HIF-1 alpha an interesting potential target in preventive and anti-cancer therapies. For instance, the compound resveratrol has demonstrated certain anti-metastatic effects on solid human colon cancer tumors due to its inhibitory effect on HIF-1 alpha expression and stabilization (Wu et al., 2008). In another study, the researcher used Novus HIF-1 alpha antibody (NB100-654) to show that the anticancer drug TAS106 acts as a potent radiosensitiser by inhibiting HIF-1alpha expression, suggesting it could be a useful agent against radiotherapy-resistant hypoxic cells in solid tumors (Yasui et al., 2008). Finally, estrogen receptor beta was successfully used to impede prostate cancer EMT by destabilizing HIF-1alpha and inhibiting VEGF-mediated SNAIL localization (Mak et al., 2010).

Novus Biologicals offers a wide selection of antibodies to HIF-1 alpha and other hypoxia related proteins that are currently being used to help advance cancer research on EMT. Additionally, all Novus antibodies are quality tested and guaranteed, with supporting data, images, publications, and reviews. Begin your hypoxia research at novusbio.com.

Yang MH, Wu KJ. TWIST activation by hypoxia inducible factor-1 (HIF-1): implications in metastasis and development. Cell Cycle. 2008 Jul 15;7(14):2090-6. [PMID: 18635960]

Liu S, Kumar SM, Martin JS, Yang R, Xu X. Snail1 mediates hypoxia-induced melanoma progression. Am J Pathol. 2011 Dec;179(6):3020-31. [PMID: 21996677]

Zhang L, Huang G, Li X, Zhang Y, Jiang Y, Shen J, Liu J, Wang Q, Zhu J, Feng X, Dong J, Qian C. Hypoxia induces epithelial-mesenchymal transition via activation of SNAI1 by hypoxia-inducible factor -1α in hepatocellular carcinoma. BMC Cancer. 2013 Mar 9;13:108. [PMID: 23496980]

Zhang W, Shi X, Peng Y, Wu M, Zhang P, Xie R, Wu Y, Yan Q, Liu S, Wang J. HIF-1α Promotes Epithelial-Mesenchymal Transition and Metastasis through Direct Regulation of ZEB1 in Colorectal Cancer. PLoS One. 2015 Jun 9;10(6):e0129603. [PMID: 26057751]

Giatromanolaki A, Koukourakis MI, Sivridis E, Pastorek J, Wykoff CC, Gatter KC, Harris AL.  Expression of hypoxia-inducible carbonic anhydrase-9 relates to angiogenic pathways and independently to poor outcome in non-small cell lung cancer. Cancer Res. 2001 Nov 1;61(21):7992-8. [PMID: 11691824]

Eckert AW, Lautner MH, Schütze A, Taubert H, Schubert J, Bilkenroth U. Coexpression of hypoxia-inducible factor-1α and glucose transporter-1 is associated with poor prognosis in oral squamous cell carcinoma patients. Histopathology. 2011 Jun;58(7):1136-47. [PMID: 21438910]

Kim BW, Cho H, Chung JY, Conway C, Ylaya K, Kim JH, Hewitt SM. Prognostic assessment of hypoxia and metabolic markers in cervical cancer using automated digital image analysis of immunohistochemistry. J Transl Med. 2013 Aug 8;11:185. [PMID: 23927384]

Wu H, Liang X, Fang Y, Qin X, Zhang Y, Liu J. Resveratrol inhibits hypoxia-induced metastasis potential enhancement by restricting hypoxia-induced factor-1 alpha expression in colon carcinoma cells. Biomed Pharmacother. 2008 Nov;62(9):613-21.[PMID: 18674879]

Yasui H, Ogura A, Asanuma T, Matsuda A, Kashiwakura I, Kuwabara M, Inanami O. Inhibition of HIF-1alpha by the anticancer drug TAS106 enhances X-ray-induced apoptosis in vitro and in vivo. Br J Cancer. 2008 Nov 4;99(9):1442-52. [PMID: 18854835]

Mak P, Leav I, Pursell B, Bae D, Yang X, Taglienti CA, Gouvin LM, Sharma VM, Mercurio AM.
ER beta impedes prostate cancer EMT by destabilizing HIF-1alpha and inhibiting VEGF-mediated snail nuclear localization: implications for Gleason grading. Cancer Cell. 2010 Apr 13;17(4):319-32. [PMID: 20385358]

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