近日，腫瘤相關(guān)研究人員發(fā)現(xiàn)一種可能導(dǎo)致肺癌發(fā)生發(fā)展的新機(jī)制,，肺癌是全球主要死亡原因之一,。
這項(xiàng)研究刊登在Genes＆Development雜志上，Sanford-Burnham醫(yī)學(xué)研究所與美國弗吉尼亞聯(lián)邦大學(xué)（VCU）,、Massey癌癥中心和研究所,、加州大學(xué)圣迭戈分校以及明尼蘇達(dá)大學(xué)分子醫(yī)學(xué)部之間共同合作完成的?？茖W(xué)家們發(fā)現(xiàn)Bax蛋白抑制因子-1(BI-1) 通過調(diào)節(jié)自噬保護(hù)肺癌細(xì)胞死亡,，自噬在機(jī)體的生理和病理過程中都能見到，在腫瘤中,，自噬打破了細(xì)胞自身組件提供腫瘤細(xì)胞生存所需的養(yǎng)分，以此來促進(jìn)腫瘤生長,。
John C. Reed醫(yī)學(xué)博士表示：癌癥細(xì)胞有“過人”地適應(yīng)性,，這一適應(yīng)性取決于各種機(jī)制，強(qiáng)大的適應(yīng)性使得腫瘤細(xì)胞得以生存和持續(xù)增長,。減少BI-1的水平,，我們就能夠調(diào)節(jié)腫瘤細(xì)胞內(nèi)的信號(hào)，減少腫瘤細(xì)胞的生存機(jī)制之一（自噬）所需的能量,，餓死肺癌細(xì)胞,。
研究人員發(fā)現(xiàn)BI-1的出現(xiàn)與鈣水平相關(guān),，鈣的存在有助于信號(hào)轉(zhuǎn)導(dǎo)。抑制BI-1會(huì)降低內(nèi)質(zhì)網(wǎng)中鈣水平，同時(shí)線粒體活性降低,，耗氧量和三磷酸腺苷（ATP）的水平也降低,。
動(dòng)物模型研究結(jié)果證實(shí)了抑制BI-1能減少人肺癌腫瘤的生長,。下一步研究計(jì)劃中,，科學(xué)家希望此項(xiàng)研究成果能應(yīng)用于篩選具有抑制BI-1介導(dǎo)的腫瘤細(xì)胞自噬功效的潛在治療藥物。（生物谷：Bioon.com）
doi:10.1101/gad.184325.111Genes&Dev.2012.26:1041-1054
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Endoplasmic reticulum protein BI-1 regulates Ca2+-mediated bioenergetics to promote autophagy
Renata Sano, Ying-Chen Claire Hou, Michael Hedvat, Ricardo G. Correa, Chih-Wen Shu, et al.
Autophagy is a lysosomal degradation pathway that converts macromolecules into substrates for energy production during nutrient-scarce conditions such as those encountered in tumor microenvironments. Constitutive mitochondrial uptake of endoplasmic reticulum (ER) Ca2+ mediated by inositol triphosphate receptors (IP3Rs) maintains cellular bioenergetics, thus suppressing autophagy. We show that the ER membrane protein Bax inhibitor-1 (BI-1) promotes autophagy in an IP3R-dependent manner. By reducing steady-state levels of ER Ca2+ via IP3Rs, BI-1 influences mitochondrial bioenergetics, reducing oxygen consumption, impacting cellular ATP levels, and stimulating autophagy. Furthermore, BI-1-deficient mice show reduced basal autophagy, and experimentally reducing BI-1 expression impairs tumor xenograft growth in vivo. BI-1's ability to promote autophagy could be dissociated from its known function as a modulator of IRE1 signaling in the context of ER stress. The results reveal BI-1 as a novel autophagy regulator that bridges Ca2+ signaling between ER and mitochondria, reducing cellular oxygen consumption and contributing to cellular resilience in the face of metabolic stress.
