Open AccessPositive feedback loop and synergistic effects between hypoxia‐inducible factor‐2α and stearoyl– C o A desaturase‐1 promote tumorigenesis in clear cell renal cell carcinoma
Author(s) -
Zhang Yujian,
Wang Hui,
Zhang Jin,
Lv Jianwei,
Huang Yiran
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12108
Subject(s) - downregulation and upregulation , carcinogenesis , clear cell renal cell carcinoma , cell growth , pi3k/akt/mtor pathway , hypoxia inducible factors , cancer research , gene knockdown , chemistry , protein kinase b , cell , biology , cancer cell , apoptosis , microbiology and biotechnology , cancer , signal transduction , medicine , biochemistry , renal cell carcinoma , gene , genetics
Adapting to hypoxic stress is pivotal in tumor progression and determining tumor malignancy. The transcriptional factor hypoxia‐inducible factor ( HIF ) is crucial in modulating tumorous hypoxic responses through altering cell energy metabolism, which includes the modification of glucose and lipid metabolism‐associated gene expression. Stearoyl– C o A desaturase‐1 ( SCD 1) is the main isoform of SCD s, the rate‐limiting enzymes in the biosynthesis of monounsaturated fatty acids from saturated fatty acids, which is extensively activated in cancer progression. In this study, we found that SCD 1 and HIF ‐2α were overexpressed in human clear cell renal cell carcinoma (cc RCC ) tissues and cc RCC cell lines, and were upregulated in the 786‐0 cc RCC cell line under hypoxia. Knockdown of SCD 1 or HIF ‐2α impacted the other's expression. Enhancing SCD 1 resulted in HIF ‐2α upregulation, which could be blocked by inhibiting the PI 3 K / A kt pathway. Deficiency of SCD 1 or HIF ‐2α in 768‐0 cells led to apoptosis, less colony formation ability, and decreased cell migration. More obvious effects were observed in 786‐0 cells with double SCD 1 and HIF ‐2α knockdown. These results indicate a PI 3 K / A kt‐mediated loop between SCD 1 and HIF ‐2α that mutually enhances their protein levels. Both SCD 1 and HIF ‐2α are critical to promoting tumorigenesis by synergistically acting on maintaining cell survival, triggering cell migration, and enhancing the colony formation ability of cancer cells.