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下调线粒体磷酸酶 PTPMT1 的表达足以促进癌细胞死亡。

Downregulation of the mitochondrial phosphatase PTPMT1 is sufficient to promote cancer cell death.

机构信息

Van Andel Research Institute, Department of Systems Biology, Grand Rapids, Michigan, United States of America.

出版信息

PLoS One. 2013;8(1):e53803. doi: 10.1371/journal.pone.0053803. Epub 2013 Jan 10.

DOI:10.1371/journal.pone.0053803
PMID:23326511
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3542197/
Abstract

Protein Tyrosine Phosphatase localized to the Mitochondrion 1 (PTPMT1) is a dual specificity phosphatase exclusively localized to the mitochondria, and has recently been shown to be a critical component in the cardiolipin biosynthetic pathway. The downregulation of PTPMT1 in pancreatic beta cells has been shown to increase cellular ATP levels and insulin production, however, the generalized role of PTPMT1 in cancer cells has not been characterized. Here we report that downregulation of PTPMT1 activity is sufficient to induce apoptosis of cancer cells. Additionally, the silencing of PTPMT1 decreases cardiolipin levels in cancer cells, while selectively increasing ATP levels in glycolytic media. Additionally, sublethal downregulation of PTPMT1 synergizes with low doses of paclitaxel to promote cancer cell death. Our data suggest that inhibition of PTPMT1 causes a metabolic crisis in cancer cells that induces cell death, and may be a mechanism by which cancer cells can be sensitized to currently available therapies.

摘要

定位于线粒体的蛋白酪氨酸磷酸酶 1（PTPMT1）是一种双重特异性磷酸酶，仅定位于线粒体，最近已被证明是心磷脂生物合成途径中的关键组成部分。胰腺β细胞中 PTPMT1 的下调已被证明可增加细胞内 ATP 水平和胰岛素的产生，然而，PTPMT1 在癌细胞中的普遍作用尚未被描述。在这里，我们报告下调 PTPMT1 的活性足以诱导癌细胞凋亡。此外，沉默 PTPMT1 可降低癌细胞中心磷脂的水平，同时选择性地增加糖酵解介质中的 ATP 水平。此外，亚致死剂量下调 PTPMT1 与低剂量紫杉醇协同作用，促进癌细胞死亡。我们的数据表明，抑制 PTPMT1 会导致癌细胞发生代谢危机，从而诱导细胞死亡，这可能是癌细胞对现有治疗方法敏感的一种机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6599/3542197/deafb8af786e/pone.0053803.g008.jpg
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