來自美國愛因斯坦醫(yī)學院的一組研究人員通過體內(nèi)和體外實驗證實，分子伴侶介導的自噬作用在腫瘤發(fā)生中起著重要的作用,，近日將其研究結(jié)果發(fā)表在《科學》（Science）雜志上,。
細胞的自噬作用在維持細胞內(nèi)環(huán)境的穩(wěn)定中起重要作用，自噬作用的2條基本通路是巨噬作用和分子伴侶介導的自噬作用（CMA）,。巨噬作用在腫瘤中的作用已經(jīng)闡明,，抑制巨噬作用可誘發(fā)腫瘤的發(fā)生。
由于正常細胞通過上調(diào)CMA通路來對抗巨噬作用的抑制,，研究者將不同腫瘤細胞中的CMA水平調(diào)至均一水平,，而不考慮巨噬作用的水平。他們還證實了在不同的人類腫瘤細胞中CMA的水平均有不同程度的上調(diào),。
在體外試驗中,，研究者發(fā)現(xiàn)CMA通過維持腫瘤細胞的代謝特征參與腫瘤細胞的增殖。隨后他們將人類肺癌移植到小鼠身上進行實驗，發(fā)現(xiàn)在體內(nèi)的腫瘤細胞也依賴于CMA,。抑制CMA后,，小鼠移植癌的生長會延遲，且轉(zhuǎn)移的數(shù)目也減少,，甚至出現(xiàn)腫瘤消退的現(xiàn)象,。后來他們又使用2種不同的黑素瘤細胞系進行實驗，也得到了同樣的結(jié)果,。
該研究結(jié)果表明,，靶向該自噬作用通路或許可為抑制腫瘤的發(fā)生提供思路。（生物谷 Bioon.com）
doi:10.1126/scitranslmed.3003182PMC:
PMID:
Chaperone-Mediated Autophagy Is Required for Tumor Growth
Maria Kon, Roberta Kiffin, Hiroshi Koga, Javier Chapochnick, Fernando Macian, Lyuba Varticovski and Ana Maria Cuervo
The 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.
