Abstract
Heat shock factor 1 (HSF1) is a major transactivator of the heat shock response. Recent studies have demonstrated that HSF1 is involved in tumor initiation, maintenance, and progression by regulating the expression of heat shock proteins (HSPs) and other molecular targets. Furthermore, HSF1 was identified as a potent proinvasion oncogene in human melanomas. However, the biological functions of HSF1 in human melanoma remain poorly understood. To determine the functional role of HSF1 in melanoma, we used short hairpin RNA (shRNA) to silence HSF1 in human melanoma cell lines and investigated its effect on cell migration and invasive ability in vitro. We found that HSF1 knockdown led to a marked reduction in migration and invasive ability, and these functions were restored by overexpression of wild-type HSF1. To confirm the in vitro results, we performed subcutaneous xenograft experiments in athymic nude mice. We found that HSF1 was required for melanoma invasion and metastasis, as well as tumorigenic potential in vivo. Overall, these results show that HSF1 is indispensable for melanoma progression and metastasis, and suggests that HSF1 could be a promising therapeutic target for melanoma.
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