Role of hypoxia-induced upregulation of caveolin-1 in hepatocellular carcinoma cell migration and invasion

Abstract

Intratumoral hypoxia occurs when cells in the inner core of solid tumor mass become deprived of oxygen. It correlates with an increased risk to develop metastasis. However, the molecular basis about the adaptation and survival of tumor cells in hypoxic environment remains obscure. Our recent data revealed that Cav1, a component of focal adhesion, is dramatically increased in metastatic hepatocellular carcinoma (HCC) cell lines and tissues, suggesting a role of Cav1 in HCC metastasis. In this study, we further investigated the potential role of Cav1 in HCC metastasis under hypoxia. Our data revealed that Cav1 mRNA and protein expressions were enhanced in various HCC cells lines when placed in hypoxic chamber or treated with hypoxic mimetic drug. Such upregulation of Cav1 was abolished with the addition of HIF1α inhibitor or depletion of HIF1α by siRNA. This suggests that hypoxia-induced Cav1 expression is HIF1α-dependent. Our findings also showed that HCC cells possessed enhanced motility under hypoxia. However, knockdown of Cav1 in HCC cells attenuated the capacity of cells to migrate and invade. Collectively, our study suggests that the increased motility of HCC cells conferred by the hypoxia-induced Cav1 expression is an adaptive mechanism of cells to survive under hypoxic stress.