No abstract

Hypoxia has been involved in the development of tumor by regulating the expression of invasiveness-associated genes. However, the specific function of hypoxia in cancer cell invasion is still unclear. The aim of the present study was to determine the role of hypoxia in invasion of prostate cancer PC3 cells and to investigate the underlying mechanisms. We found that hypoxia significantly increased the invasive activity of PC3 cells, via up-regulation of the expression of hypoxia inducible factor 1α (HIF-1α) and the autocrine production of tumor necrosis factor α (TNF-α). More important, TNF-α cooperated with HIF-1α in promoting stabilization of Snail, a transcriptional repressor of E-cadherin expression, which lead to the up-regulation of invasiveness-associated genes MMP-9, fibronectin and vimentin. Snail silencing by specific siRNA significantly inhibited hypoxia-induced invasion of PC3 cells, indicating an essential role of Snail in conferring the malignant phenotype to cancer cells under hypoxic conditions. In conclusion, our data demonstrate that hypoxia promoted the invasiveness of prostate cancer PC3 cells via HIF-1α- and TNF-α-induced stabilization of Snail, suggesting a signaling mechanism involving HIF-1α/TNF-α/Snail that mediates invasiveness hypoxic tumor cells in the absence of neoangiogenesis.

Renal cell carcinoma (RCC) is a common form of urological tumors, accounting for nearly 3% of human malignancies worldwide. 1 Based on histological and cytogenetic features, clear cell renal cell carcinoma (ccRCC) has been demonstrated to be the most common subtype of RCC. 2 Due to resistance to traditional chemo-and radiotherapeutic strategies, surgical removal is still the primary treatment option for ccRCC. However, ccRCC patients exhibit a poor prognosis owing to the high incidence of recurrence and metastasis. Approximately 25% of ccRCC patients will experience local