HIG2 promotes colorectal cancer progression via hypoxia-dependent and independent pathways

Sun Hee Kim; Dingzhi Wang; Yun Yong Park; Hiroshi Katoh; Ofer Margalit; Michal Sheffer; Hong Wu; Vijaykumar R. Holla; Ju Seog Lee; Raymond N. DuBois

doi:10.1016/j.canlet.2013.07.028

HIG2 promotes colorectal cancer progression via hypoxia-dependent and independent pathways

Sun Hee Kim, Dingzhi Wang, Yun Yong Park, Hiroshi Katoh, Ofer Margalit, Michal Sheffer, Hong Wu, Vijaykumar R. Holla, Ju Seog Lee, Raymond N. DuBois

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

HIG2 (hypoxia-inducible gene 2) is a biomarker of hypoxia and elevated in several cancers. Here, we show that HIG2 also upregulated HIF-1α expression under hypoxic conditions and enhanced AP-1 expression under normoxic conditions, which affects colorectal cancer cell survival. Importantly, over-expression of HIG2 promoted tumor growth by suppressing apoptosis in a mouse orthotopic model. These results are likely relevant to human disease since we found that the expression of HIG2 is gradually elevated as tumors progress. Collectively, these findings suggest that HIG2 plays an important role in promoting colorectal cancer growth in hypoxia-dependent and independent manners.

Original language	English (US)
Pages (from-to)	159-165
Number of pages	7
Journal	Cancer Letters
Volume	341
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2013.07.028
State	Published - Dec 1 2013

Keywords

Colorectal cancer
HIF-1α
HIG2
Hypoxia
Normoxia
Survival

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.canlet.2013.07.028

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title = "HIG2 promotes colorectal cancer progression via hypoxia-dependent and independent pathways",

abstract = "HIG2 (hypoxia-inducible gene 2) is a biomarker of hypoxia and elevated in several cancers. Here, we show that HIG2 also upregulated HIF-1α expression under hypoxic conditions and enhanced AP-1 expression under normoxic conditions, which affects colorectal cancer cell survival. Importantly, over-expression of HIG2 promoted tumor growth by suppressing apoptosis in a mouse orthotopic model. These results are likely relevant to human disease since we found that the expression of HIG2 is gradually elevated as tumors progress. Collectively, these findings suggest that HIG2 plays an important role in promoting colorectal cancer growth in hypoxia-dependent and independent manners.",

keywords = "Colorectal cancer, HIF-1α, HIG2, Hypoxia, Normoxia, Survival",

author = "Kim, {Sun Hee} and Dingzhi Wang and Park, {Yun Yong} and Hiroshi Katoh and Ofer Margalit and Michal Sheffer and Hong Wu and Holla, {Vijaykumar R.} and Lee, {Ju Seog} and DuBois, {Raymond N.}",

note = "Funding Information: This work is supported by NIH Grants RO1DK 62112 (R.N.D), P01-CA-77839 (R.N.D), and R37-DK47297 (R.N.D). R.N.D. D.W. and S.H.K. designed this research project; S.H.K. performed most of the experiments; H.K., O.M., and H.W contributed to establish the orthotopic mouse model; Y.Y.P, M.S. and J.S.L conducted the microarray analysis for human tissues and cell samples; V.R collected mRNA from human tissue. S.H.K. wrote the manuscript with D.W.{\textquoteright}s help; and R.N.D. supervised the project. ",

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T1 - HIG2 promotes colorectal cancer progression via hypoxia-dependent and independent pathways

AU - Kim, Sun Hee

AU - Wang, Dingzhi

AU - Park, Yun Yong

AU - Katoh, Hiroshi

AU - Margalit, Ofer

AU - Sheffer, Michal

AU - Wu, Hong

AU - Holla, Vijaykumar R.

AU - Lee, Ju Seog

AU - DuBois, Raymond N.

N1 - Funding Information: This work is supported by NIH Grants RO1DK 62112 (R.N.D), P01-CA-77839 (R.N.D), and R37-DK47297 (R.N.D). R.N.D. D.W. and S.H.K. designed this research project; S.H.K. performed most of the experiments; H.K., O.M., and H.W contributed to establish the orthotopic mouse model; Y.Y.P, M.S. and J.S.L conducted the microarray analysis for human tissues and cell samples; V.R collected mRNA from human tissue. S.H.K. wrote the manuscript with D.W.’s help; and R.N.D. supervised the project.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - HIG2 (hypoxia-inducible gene 2) is a biomarker of hypoxia and elevated in several cancers. Here, we show that HIG2 also upregulated HIF-1α expression under hypoxic conditions and enhanced AP-1 expression under normoxic conditions, which affects colorectal cancer cell survival. Importantly, over-expression of HIG2 promoted tumor growth by suppressing apoptosis in a mouse orthotopic model. These results are likely relevant to human disease since we found that the expression of HIG2 is gradually elevated as tumors progress. Collectively, these findings suggest that HIG2 plays an important role in promoting colorectal cancer growth in hypoxia-dependent and independent manners.

AB - HIG2 (hypoxia-inducible gene 2) is a biomarker of hypoxia and elevated in several cancers. Here, we show that HIG2 also upregulated HIF-1α expression under hypoxic conditions and enhanced AP-1 expression under normoxic conditions, which affects colorectal cancer cell survival. Importantly, over-expression of HIG2 promoted tumor growth by suppressing apoptosis in a mouse orthotopic model. These results are likely relevant to human disease since we found that the expression of HIG2 is gradually elevated as tumors progress. Collectively, these findings suggest that HIG2 plays an important role in promoting colorectal cancer growth in hypoxia-dependent and independent manners.

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KW - Hypoxia

KW - Normoxia

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HIG2 promotes colorectal cancer progression via hypoxia-dependent and independent pathways

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