近日，懷特黑德研究所研究人員發(fā)現(xiàn),，一個(gè)特定的基因表達(dá)增加后會(huì)促進(jìn)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(xué)家識(shí)別基因表達(dá)圖譜預(yù)測(cè)患者的治療效果和治療反應(yīng),，也可以引導(dǎo)開發(fā)針對(duì)多種類型癌癥的療法,。
在正常細(xì)胞中，各種壓力包括熱,、缺氧,、毒素會(huì)激活熱休克因子1(HSF1)，導(dǎo)致所謂的熱休克或伴侶蛋白質(zhì)表達(dá)增加,，以保持應(yīng)激細(xì)胞內(nèi)穩(wěn)態(tài),?？茖W(xué)家們已經(jīng)知道許多癌細(xì)胞具有更高水平的伴侶蛋白，這些蛋白質(zhì)是腫瘤細(xì)胞生存和增殖的重要因素,。
然而現(xiàn)在,，研究人員報(bào)告稱HSF1不僅增加癌癥伴侶蛋白表達(dá)，同時(shí)調(diào)節(jié)范圍相當(dāng)廣泛,，對(duì)腫瘤細(xì)胞的惡性行為也有調(diào)控作用,。HSF1的活性會(huì)促進(jìn)三個(gè)最普遍癌癥類型：乳腺癌、肺癌,、結(jié)腸癌的發(fā)展。這項(xiàng)研究結(jié)果發(fā)表在Cell雜志上,。
除了證實(shí)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(xì)胞中會(huì)變得活躍,。
這說明它不是簡(jiǎn)單地在腫瘤遭遇環(huán)境壓力情況下，驅(qū)動(dòng)HSF1的活性,，而是連接到HSF1激活癌細(xì)胞的核心區(qū)域,，促發(fā)一個(gè)獨(dú)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(gè)潛在的治療靶標(biāo),。（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.
