近日,，懷特黑德研究所研究人員發(fā)現(xiàn)，一個特定的基因表達增加后會促進乳腺癌,、結(jié)腸癌和肺癌患者的轉(zhuǎn)移和死亡,。這一發(fā)現(xiàn)不僅有助于科學家識別基因表達圖譜預測患者的治療效果和治療反應，也可以引導開發(fā)針對多種類型癌癥的療法,。
在正常細胞中,，各種壓力包括熱、缺氧,、毒素會激活熱休克因子1(HSF1),，導致所謂的熱休克或伴侶蛋白質(zhì)表達增加，以保持應激細胞內(nèi)穩(wěn)態(tài),?？茖W家們已經(jīng)知道許多癌細胞具有更高水平的伴侶蛋白，這些蛋白質(zhì)是腫瘤細胞生存和增殖的重要因素,。
然而現(xiàn)在,，研究人員報告稱HSF1不僅增加癌癥伴侶蛋白表達，同時調(diào)節(jié)范圍相當廣泛,，對腫瘤細胞的惡性行為也有調(diào)控作用,。HSF1的活性會促進三個最普遍癌癥類型：乳腺癌、肺癌,、結(jié)腸癌的發(fā)展,。這項研究結(jié)果發(fā)表在Cell雜志上。
除了證實這種基因激活程序與熱休克蛋白不同,，研究人員發(fā)現(xiàn),，在許多腫瘤中，它在幾乎所有腫瘤細胞中會變得活躍,。
這說明它不是簡單地在腫瘤遭遇環(huán)境壓力情況下,，驅(qū)動HSF1的活性，而是連接到HSF1激活癌細胞的核心區(qū)域，促發(fā)一個獨特的基因調(diào)控程序,，使得腫瘤獲得侵略性表型,。這表明HSF1本身可能是一個潛在的治療靶標。（生物谷：Bioon.com）
編譯自：Heat-shock factor reveals its unique role in supporting highly malignant cancers
doi:10.1016/j.cell.2012.06.031
PMC:
PMID:
HSF1 Drives a Transcriptional Program Distinct from Heat Shock to Support Highly Malignant Human Cancers
Marc L. Mendillo, Sandro Santagata, Martina Koeva, George W. Bell, Rong Hu, Rulla M. Tamimi, Ernest Fraenkel, et al.
Heat-Shock Factor 1 (HSF1), master regulator of the heat-shock response, facilitates malignant transformation, cancer cell survival, and proliferation in model systems. The common assumption is that these effects are mediated through regulation of heat-shock protein (HSP) expression. However, the transcriptional network that HSF1 coordinates directly in malignancy and its relationship to the heat-shock response have never been defined. By comparing cells with high and low malignant potential alongside their nontransformed counterparts, we identify an HSF1-regulated transcriptional program specific to highly malignant cells and distinct from heat shock. Cancer-specific genes in this program support oncogenic processes: cell-cycle regulation, signaling, metabolism, adhesion and translation. HSP genes are integral to this program, however, many are uniquely regulated in malignancy. This HSF1 cancer program is active in breast, colon and lung tumors isolated directly from human patients and is strongly associated with metastasis and death. Thus, HSF1 rewires the transcriptome in tumorigenesis, with prognostic and therapeutic implications.
