title: Downregulation of the mitochondrial phosphatase PTPMT1 is sufficient to promote cancer cell death.
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.
authors: Van Andel Research Institute, Department of Systems Biology, Grand Rapids, Michigan, United States of America.
authors: Natalie M
authors: NM
authors: Niemi
authors: Nathan J
authors: NJ
authors: Lanning
authors: Laura M
authors: LM
authors: Westrate
authors: Jeffrey P
authors: JP
authors: MacKeigan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002308:Cardiolipins / Q000378:metabolism; D016923:Cell Death / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage
chemical_list: D002308:Cardiolipins; D000255:Adenosine Triphosphate; D051059:PTEN Phosphohydrolase; D017239:Paclitaxel