Heat shock factor 1 is required for migration and invasion of human melanoma in vitro and in vivo
Heat shock factor 1 is required for migration and invasion of human melanoma in vitro and in vivo
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DOI：
10.1016/j.canlet.2014.08.029
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发表时间：
2014-11-28
期刊：
影响因子：
9.7
通讯作者：
Muto, Masahiko
中科院分区：
文献类型：
--
作者：
Nakamura, Yoshitaka;Fujimoto, Mitsuaki;Muto, Masahiko
热休克因子1（HSF 1）是热休克反应的主要反式激活因子。最近的研究表明，HSF1通过调节热休克蛋白（HSPs）和其他分子靶点的表达参与肿瘤的发生、维持和进展。此外，HSF 1被鉴定为人类黑色素瘤中的有效促侵袭癌基因。然而，HSF1在人类黑色素瘤中的生物学功能仍然知之甚少。为了确定HSF1在黑色素瘤中的功能作用，我们使用短发夹RNA（shRNA）沉默人黑色素瘤细胞系中的HSF1，并研究其对细胞迁移和体外侵袭能力的影响。我们发现，HSF1敲低导致迁移和侵袭能力的显着降低，这些功能通过野生型HSF1的过表达而恢复。为了证实体外结果，我们在无胸腺裸鼠中进行皮下异种移植实验。我们发现HSF1是黑色素瘤侵袭和转移以及体内致瘤潜力所必需的。总之，这些结果表明，HSF 1是黑色素瘤的进展和转移所不可或缺的，并表明HSF 1可能是黑色素瘤的一个有前途的治疗靶点。(C)2014爱思唯尔爱尔兰有限公司版权所有。
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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.