Open Access15‐LOX‐1 suppression of hypoxia‐induced metastatic phenotype and HIF‐1 α expression in human colon cancer cells
Author(s) -
Wu Yuanqing,
Mao Fei,
Zuo Xiangsheng,
Moussalli Micheline J.,
Elias Elias,
Xu Weiguo,
Shureiqi Imad
Publication year - 2014
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.222
Subject(s) - angiogenesis , cancer research , metastasis , carcinogenesis , colorectal cancer , cancer cell , cancer , hypoxia (environmental) , downregulation and upregulation , hif1a , biology , vascular endothelial growth factor , medicine , chemistry , vegf receptors , biochemistry , organic chemistry , oxygen , gene
The expression of 15‐lipoxygenase‐1 (15‐ LOX ‐1) is downregulated in colon cancer and other major cancers, and 15‐ LOX ‐1 reexpression in cancer cells suppresses colonic tumorigenesis. Various lines of evidence indicate that 15‐ LOX ‐1 expression suppresses premetastatic stages of colonic tumorigenesis; nevertheless, the role of 15‐ LOX ‐1 loss of expression in cancer epithelial cells in metastases continues to be debated. Hypoxia, a common feature of the cancer microenvironment, promotes prometastatic mechanisms such as the upregulation of hypoxia‐inducible factor ( HIF )‐1 α , a transcriptional master regulator that enhances cancer cell metastatic potential, angiogenesis, and tumor cell invasion and migration. We have, therefore, tested whether restoring 15‐ LOX ‐1 in colon cancer cells affects cancer cells' hypoxia response that promotes metastasis. We found that 15‐ LOX ‐1 reexpression in HCT 116, HT 29 LMM , and LoVo colon cancer cells inhibited survival, vascular endothelial growth factor ( VEGF ) expression, angiogenesis, cancer cell migration and invasion, and HIF ‐1 α protein expression and stability under hypoxia. These findings demonstrate that 15‐ LOX ‐1 expression loss in cancer cells promotes metastasis and that therapeutically targeting ubiquitous 15‐ LOX ‐1 loss in cancer cells has the potential to suppress metastasis.