癌细胞的“自我进食”策略可能会成为治疗它的关键点

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在胰腺癌的常见前体病变(PanIN)中可以看到NIX蛋白活性(褐色染色)的证据。 NIX活性在胰腺导管腺癌(PDAC)中升高,胰腺导管腺癌是最常见的胰腺癌。 NIX直接负责触发线粒体线粒体自噬或“自我喂养”。

癌细胞使用奇怪的策略在肿瘤的低能量环境中繁殖;他们摧毁了自己的线粒体!冷泉港实验室(CSHL)的研究人员也知道这是如何发生的,并为胰腺癌的治疗提供了一个有希望的新目标。

为什么癌细胞会破坏正常功能的线粒体? “这可能看似违反直觉,”MD-Ph.D承认。学生Brinda Alagesan,David Tuveson博士是CSHL实验室的成员。

根据Alagesan的说法,考虑癌细胞的最简单方法可能是将线粒体作为一种动力装置。 “线粒体是细胞的发源地,”她回忆说,回忆起普通小学的课程。像传统的动力装置一样,线粒体会造成污染。

“这些有害的副产品或污染物被称为活性氧或ROS,”Alagesan补充说。 “它们中的许多都可能对细胞造成损害。我们认为[通过食用自己的线粒体]胰腺癌细胞正在减少这些有害ROS的产生,同时仍能产生足够的能量来增殖。”

这仍然是一个假设,但它可以解释为什么胰腺癌细胞容易发生线粒体自噬或自体线粒体自噬。

In the Journal of Cancer Discovery, Alagesan and co-lead author Dr. Timothy Humpton describe what happens when a protein called KRAS becomes active in the unique nutrient depletion environment of pancreatic tumors. KRAS begins a "signal cascade" that causes cells to eat their own mitochondria and transfer glucose and glutamine from the remaining mitochondria. These transferred nutrients are used to support cell division.

"I ideally want to directly suppress cancer that promotes KRAS protein, but unfortunately no one has been able to do this in a clinically relevant way so far," Alagesan explained.

A pathway leading to an increase in protein NIX. NIX is directly responsible for triggering the mitochondrial autophagy phase, which seems to be critical for cancer cell proliferation.

"The results of mice tell us that by inhibiting the NIX pathway, we may prevent cancer cells from using energy to proliferate in the way they need," Alagesan said.

The Tuveson team is now turning its attention to destroying this same NIX pathway in human pancreatic cancer cells and applying it to clinical trial design. #清风计划#

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