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KMID : 0578320190420080604
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Molecules and Cells
2019 Volume.42 No. 8 p.604 ~ p.616
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Phosphoserine Phosphatase Promotes Lung Cancer Progression through the Dephosphorylation of IRS-1 and a Noncanonical L-Serine-Independent Pathway
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Park Seong-Min
Seo Eun-Hye
Bae Dong-Hyuck
Kim Sung-Soo
Kim Jina
Lin Weiwei
Kim Kyung-Hee
Park Jong-Bae
Kim Yong-Sung
Yin Jinlong
Kim Seon-Young
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Abstract
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Phosphoserine phosphatase (PSPH) is one of the key enzymes of the L-serine synthesis pathway. PSPH is reported to affect the progression and survival of several cancers in an L-serine synthesis-independent manner, but the mechanism remains elusive. We demonstrate that PSPH promotes lung cancer progression through a noncanonical L-serine-independent pathway. PSPH was significantly associated with the prognosis of lung cancer patients and regulated the invasion and colony formation of lung cancer cells. Interestingly, L-serine had no effect on the altered invasion and colony formation by PSPH. Upon measuring the phosphatase activity of PSPH on a serine-phosphorylated peptide, we found that PSPH dephosphorylated phospho-serine in peptide sequences. To identify the target proteins of PSPH, we analyzed the protein phosphorylation profile and the PSPH-interacting protein profile using proteomic analyses and found one putative target protein, IRS-1. Immunoprecipitation and immunoblot assays validated a specific interaction between PSPH and IRS1 and the dephosphorylation of phospho-IRS-1 by PSPH in lung cancer cells. We suggest that the specific interaction and dephosphorylation activity of PSPH have novel therapeutic potential for lung cancer treatment, while the metabolic activity of PSPH, as a therapeutic target, is controversial.
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KEYWORD
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IRS-1, L-serine independent pathway, lung cancer, phosphoserine phosphatase
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