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Low-Molecular-Weight Protein Tyrosine Phosphatase Promotes Prostate Cancer Growth and Metastasis

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Abstract

Currently, prostate adenocarcinoma (PRAD) is the second most common cancer in males, and the metastatic progression of prostate tumors to the bone accounts for a large majority of prostate cancer-related deaths. As such, identifying potential therapeutic targets to prevent prostate cancer progression proves to be vital. The low-molecular-weight protein tyrosine phosphatase (LMPTP) has been found to be highly expressed in metastatic hormone-naïve prostate cancer patients and is associated with lower survival rates. However, the molecular mechanism by which LMPTP promotes prostate cancer growth and metastatic development remains unclear. In this paper, we confirmed the oncogenic nature of LMPTP in prostate cancer growth in vitro and in vivo using both CRISPR-Cas9-mediated knockout (KO) of LMPTP and inhibition of LMPTP via an orally bio-available LMPTP inhibitor. Additionally, the use of a soft agar colony formation assay, Matrigel invasion chamber assay, and in vivo intraosseous metastasis model further implicated LMPTP in metastatic prostate cancer development. Through phosphoproteomic and metabolomic analyses we uncovered a possible glutathione deficiency and compensatory model in LMPTP KO cells that would explain the role of LMPTP in prostate cancer progression. Our findings implicate LMPTP in prostate cancer progression which taken together with our confirmation that loss of LMPTP responds synergistically with current prostate cancer drugs establishes LMPTP as a potential drug target for prostate cancer patients.

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This item is under embargo until January 11, 2024.