Lockdown, a selective small-molecule inhibitor of the integrin phosphatase PPM1F, blocks cancer cell invasion

Grimm, Tanja; Herbinger, Marleen; Krüger, Lena; Muller, Sylviane; Mayer, Thomas; Hauck, Christof R.

doi:10.1016/j.chembiol.2022.03.011

Cited by 5 publications

(1 citation statement)

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“…Integrins, heterodimers protein composed by α and β chains, are important adhesion molecules with dynamic regulatory functions [21]. Cell adhesion is essential for organ formation, cell migration, and extracellular matrix interactions [21][22][23]. ITGB1 is one of the important integrin members.…”

Section: Introductionmentioning

confidence: 99%

PPM1F regulates ovarian cancer progression by affecting the dephosphorylation of ITGB1

Leng,

Li,

et al. 2023

Preprint

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Background PPM1F has been shown to play diverse biological functions in the progression of multiple tumors. PPM1F controls the T788/T789 phosphorylation switch of ITGB1 and regulates integrin activity. However, the impacts of PPM1F and ITGB1 on ovarian cancer (OV) progression remain unclear. whether there is such a regulatory relationship between PPM1F and ITGB1 in ovarian cancer has not been studied. Therefore, the purpose of this study is to elucidate the function and mechanism of PPM1F in ovarian cancer. Methods The expression level and survival curve of PPM1F were analyzed by databases. Gain of function and loss of function were applied to explore the function of PPM1F in ovarian cancer. Tumor formation assay in nude mice showed that knockdown of PPM1F inhibited tumor formation. We testified the effect of PPM1F on ITGB1 dephosphorylation in ovarian cancer cells by co-immunoprecipitation and western blotting. Loss of function was applied to investigate the function of ITGB1 in ovarian cancer. ITGB1-mut overexpression promotes the progression of ovarian cancer. Rescue assays showed the promoting effect of ITGB1-wt on ovarian cancer is attenuated due to the dephosphorylation of ITGB1-wt by PPM1F. Results PPM1F and ITGB1 play an oncogene function in ovarian cancer. PPM1F regulates the phosphorylation of ITGB1, which affects the occurrence and development of ovarian cancer.

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