Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis
Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis
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DOI：
10.1016/j.cell.2007.07.020
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发表时间：
2007-09-21
期刊：
影响因子：
64.5
通讯作者：
Lindquist, Susan
中科院分区：
文献类型：
--
作者：
Dai, Chengkai;Whitesell, Luke;Lindquist, Susan
热休克因子1（HSF 1）是真核生物中热休克反应的主要调节因子，是一种高度保守的保护机制。HSF 1功能在许多病理生理条件下增加存活。它如何参与恶性肿瘤仍然是未知的。我们报告说，消除HSF 1保护小鼠免受RAS癌基因突变或肿瘤抑制基因p53热点突变引起的肿瘤。在细胞培养中，HSF 1通过协调核心细胞功能网络（包括增殖、存活、蛋白质合成和葡萄糖代谢）支持恶性转化。HSF 1对致癌转化的显著影响并不限于小鼠系统或肿瘤起始;不同来源的人类癌细胞系显示出比非转化对应物更大的对HSF 1功能的依赖性，以维持增殖和存活。虽然在大多数情况下，HSF 1可以增强生物体的存活和寿命，但它在支持癌症的致命现象方面具有相反的作用。
Heat shock factor 1 ( HSF1) is the master regulator of the heat shock response in eukaryotes, a very highly conserved protective mechanism. HSF1 function increases survival under a great many pathophysiological conditions. How it might be involved in malignancy remains largely unexplored. We report that eliminating HSF1 protects mice from tumors induced by mutations of the RAS oncogene or a hot spot mutation in the tumor suppressor p53. In cell culture, HSF1 supports malignant transformation by orchestrating a network of core cellular functions including proliferation, survival, protein synthesis, and glucose metabolism. The striking effects of HSF1 on oncogenic transformation are not limited to mouse systems or tumor initiation; human cancer lines of diverse origins show much greater dependence on HSF1 function to maintain proliferation and survival than their nontransformed counterparts. While it enhances organismal survival and longevity under most circumstances, HSF1 has the opposite effect in supporting the lethal phenomenon of cancer.