近日，肿瘤相关研究人员发现一种可能导致肺癌发生发展的新机制，肺癌是全球主要死亡原因之一。
这项研究刊登在Genes＆Development杂志上，Sanford-Burnham医学研究所与美国弗吉尼亚联邦大学（VCU）、Massey癌症中心和研究所、加州大学圣迭戈分校以及明尼苏达大学分子医学部之间共同合作完成的。科学家们发现Bax蛋白抑制因子-1(BI-1) 通过调节自噬保护肺癌细胞死亡，自噬在机体的生理和病理过程中都能见到，在肿瘤中，自噬打破了细胞自身组件提供肿瘤细胞生存所需的养分，以此来促进肿瘤生长。
John C. Reed医学博士表示：癌症细胞有“过人”地适应性，这一适应性取决于各种机制，强大的适应性使得肿瘤细胞得以生存和持续增长。减少BI-1的水平，我们就能够调节肿瘤细胞内的信号，减少肿瘤细胞的生存机制之一（自噬）所需的能量，饿死肺癌细胞。
研究人员发现BI-1的出现与钙水平相关，钙的存在有助于信号转导。抑制BI-1会降低内质网中钙水平，同时线粒体活性降低，耗氧量和三磷酸腺苷（ATP）的水平也降低。
动物模型研究结果证实了抑制BI-1能减少人肺癌肿瘤的生长。下一步研究计划中，科学家希望此项研究成果能应用于筛选具有抑制BI-1介导的肿瘤细胞自噬功效的潜在治疗药物。（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.
