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本帖最后由 细胞海洋 于 2011-11-22 10:09 编辑
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作者：Ana Cuervo 来源：《科学—转化医学》 发布时间：2011-11-20
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美国研究人员发现，癌细胞生长能量源自机体回收利用蛋白质的过程。小鼠实验显示，阻断这一过程，肿瘤开始萎缩，癌细胞几乎不再转移。
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这项研究有助开发治癌新药，关键是如何有选择地抑制机体回收利用蛋白质。! d8 g/ x R/ a! Z- g6 n
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' \0 Y' c8 P x/ X ^# ~研究人员先前知道，癌细胞需要耗用大量葡萄糖，作为支撑非正常快速生长和分裂的能量，却不清楚癌细胞如何获取所需能量。5 s; a. V; D& H/ |: ?$ j" |
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最新研究显示，癌细胞以加快细胞自噬方式获取能量。细胞自噬是机体一种重要防御和保护机制，是把受损、变性或衰老的蛋白质以及细胞器运输至溶酶体，继而消化降解的过程。
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耶希瓦大学爱因斯坦医学院发展分子生物学教授安娜·库埃沃告诉记者：“溶酶体不仅是垃圾箱，更像小型回收站。在那里，细胞残骸转变成能量。癌细胞似乎知道如何优化这一进程，以获取所需能量。”
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; l ~8 N2 g6 t$ z库埃沃及其同事在40多种人体肺部、乳腺和肝脏肿瘤细胞中发现，分子伴侣介导的自噬水平高于正常状态，而肿瘤周边正常组织的这一类型自噬处于水平正常。
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抑自噬
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“我们改变基因，阻断这一回收利用进程，癌细胞随即停止分裂，大部分死亡，”库埃沃说，“我们还把这种方法运用于小鼠，结果小鼠的肿瘤显著萎缩，几乎完全停止转移。”3 Y$ u$ p$ y7 ]' b5 Y# P
; k. y+ h4 d& o研究人员认为，有选择地阻断癌细胞分子伴侣介导的自噬可能成为缩小肿瘤、阻止癌细胞转移的“有效策略”。
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库埃沃说：“今后研究中，我们希望开发药物，以实现操纵基因达成的效果；我们同时将继续探索如何用基因操纵手段治疗不同类型的肺癌。”
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阻转移& F4 u+ ]/ Q. Y( a0 W+ m7 g3 M
. X/ ^0 x# n- _3 o: A2 R这项研究所获结果由最新一期美国《科学—转化医学》杂志发表。; ]( S+ I- b/ h% n4 x3 O
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美国科罗拉多大学的安德鲁·索伯恩教授和加利福尼亚大学旧金山分校的贾延塔·德布纳特认为，研究结果“激动人心”。+ n$ P' x0 B7 R3 l3 C2 ]2 }
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他们说，分子伴侣介导的自噬抑制剂可能有助治疗癌症，因为它们可能抑制肿瘤生长，弱化癌细胞转移能力。" b$ e$ x9 G4 v
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不过，索伯恩和德布纳特说，迄今为止，“就选择地抑制病患体内分子伴侣介导的自噬，没有可行方法”。（来源：新华网 黄敏） ; s2 j( Z% e, K+ D4 W; K2 m
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% e2 H6 t( n& x' V/ f, s8 r6 p% \Sci Transl Med 16 November 2011:
5 o: ?7 V3 C( Q- [* f G0 c6 YVol. 3, Issue 109, p. 109ra117 9 g7 x' H- l3 V4 Y
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3003182 6 f" e/ `( Z7 p h- P4 ?2 k
Research Article 6 u1 O6 l( N( U/ i. Q1 o# m4 W
Cancer- c3 v- @ n% l( ^3 Q
Chaperone-Mediated Autophagy Is Required for Tumor Growth' f4 w8 y% v. I# o' D4 }
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Maria Kon1, Roberta Kiffin1, Hiroshi Koga1, Javier Chapochnick2, Fernando Macian3,4, Lyuba Varticovski5 and Ana Maria Cuervo1,4,6,* ' X& c- ?: ~! s# J2 N, O
+ Author Affiliations6 _7 P4 O$ R* `) r) x
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1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. " N. a+ E8 a% z
2Department of Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
* u3 W/ @# a& a5 D3Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. 4 d, S, B9 G( ]
4Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
2 I: N- I1 E4 Q6 I' B' W5Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. 1 b" |2 F* a+ W1 d
6Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
4 @ o2 |* x9 S, ^, P, Z8 B↵*To whom correspondence should be addressed. E-mail: ana-maria.cuervo@einstein.yu.edu
% v% J* ~( j- b* M: {# VAbstract
+ j! u5 w2 H6 h# A6 |, aThe cellular process of autophagy (literally “self-eating”) is important for maintaining the homeostasis and bioenergetics of mammalian cells. Two of the best-studied mechanisms of autophagy are macroautophagy and chaperone-mediated autophagy (CMA). Changes in macroautophagy activity have been described in cancer cells and in solid tumors, and inhibition of macroautophagy promotes tumorigenesis. Because normal cells respond to inhibition of macroautophagy by up-regulation of the CMA pathway, we aimed to characterize the CMA status in different cancer cells and to determine the contribution of changes in CMA to tumorigenesis. Here, we show consistent up-regulation of CMA in different types of cancer cells regardless of the status of macroautophagy. We also demonstrate an increase in CMA components in human cancers of different types and origins. CMA is required for cancer cell proliferation in vitro because it contributes to the maintenance of the metabolic alterations characteristic of malignant cells. Using human lung cancer xenografts in mice, we confirmed the CMA dependence of cancer cells in vivo. Inhibition of CMA delays xenograft tumor growth, reduces the number of cancer metastases, and induces regression of existing human lung cancer xenografts in mice. The fact that similar manipulations of CMA also reduce tumor growth of two different melanoma cell lines suggests that targeting this autophagic pathway may have broad antitumorigenic potential. : G, B# b, J# y' m; m* B4 F# Y
) _3 t( u1 K% J: X6 u- d9 P2 nCopyright © 2011, American Association for the Advancement of Science
. `4 ]1 c3 q/ H$ o# v% ZCitation: M. Kon, R. Kiffin, H. Koga, J. Chapochnick, F. Macian, L. Varticovski, A. M. Cuervo, Chaperone-Mediated Autophagy Is Required for Tumor Growth. Sci. Transl. Med. 3, 109ra117 (2011).! _- u6 o4 T# Z/ r+ }( u! n) E
; Y9 C% n1 ^% ]. Y8 x5 i( H http://stm.sciencemag.org/content/3/109/109ra117.abstract: Q3 u9 D* W; Y0 V& b2 h- l$ m1 _5 {
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发表于 2011-11-20 22:17
发表于 2011-11-21 09:28
