Amaravadi Ravi K
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
J Clin Invest. 2008 Dec;118(12):3837-40. doi: 10.1172/JCI37667. Epub 2008 Nov 20.
Autophagy--a process of "self-eating" that involves enzymatic digestion and recycling of cellular constituents in response to stress--contributes to both cancer cell death and survival. In this issue of the JCI, Lu et al. report that controlled induction of tumor suppressor gene aplasia Ras homolog member I (ARHI) results in autophagic cell death of human ovarian cancer cells in vitro (see the related article beginning on page 3917). However, within xenograft tumors in mice, multiple factors within the tumor microenvironment switched ARHI-induced autophagy to a mechanism of tumor cell survival, leading to tumor dormancy. Since ARHI expression is suppressed in the majority of breast and ovarian cancers but is high in premalignant lesions, ARHI-induced autophagy could be manipulated for therapeutic benefit.
自噬——一种“自我吞噬”过程,涉及在应激反应下对细胞成分进行酶促消化和循环利用——既有助于癌细胞死亡,也有助于其存活。在本期《临床研究杂志》中,卢等人报告称,可控诱导肿瘤抑制基因发育不全Ras同源成员I(ARHI)会导致人卵巢癌细胞在体外发生自噬性细胞死亡(见第3917页开始的相关文章)。然而,在小鼠异种移植肿瘤中,肿瘤微环境中的多种因素将ARHI诱导的自噬转变为肿瘤细胞存活机制,导致肿瘤休眠。由于ARHI表达在大多数乳腺癌和卵巢癌中受到抑制,但在癌前病变中较高,因此可以通过操纵ARHI诱导的自噬来获得治疗益处。