PASD1 promotes STAT3 activity and tumor growth by inhibiting TC45-mediated dephosphorylation of STAT3 in the nucleus.

Activation of the transcription factor signal transducer and activator of transcription 3 is tightly regulated during various physiological processes, such as cell proliferation, survival, and differentiation, and aberrant activation results in tumorigenesis. In this study, we identified the cancer/testis antigen PASD1 as a positive regulator of duanyu18133 activity. Overexpression of PASD1 activated duanyu18133 and potentiated IL-6-induced activation of whereas knockdown of PASD1 had opposite effects. Endogenous coimmunoprecipitation experiments indicated that PASD1 interacted with duanyu18133 in the nucleus. Overexpression of PASD1 enhanced both basal and IL-6-induced duanyu18133 phosphorylation at Y705, whereas knockdown of PASD1 had opposite effects. Mechanistically, PASD1 competed with TC45, a nuclear protein tyrosine phosphatase, to associate with duanyu18133, thus inhibited TC45-mediated dephosphorylation of Consistently, knockdown of PASD1 inhibited expression of many pro-oncogenic genes, leading to suppression of cell proliferation, anchorage-independent growth, cell migration, and tumor growth in nude mice. Our findings demonstrate that PASD1 serves as a critical nuclear positive regulator of gene expression and tumorigenesis.

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