Protein phosphatase 1B dephosphorylates Rho guanine nucleotide dissociation inhibitor 1 and suppresses cancer cell migration and invasion

Cancer Letters
Hee Jun ChoHee Gu Lee

Abstract

Rho GTPases control a wide range of cellular processes, and their deregulation is associated with promotion of an aggressive and metastatic tumor phenotype in human cancers. Rho guanine nucleotide dissociation inhibitor 1 (RhoGDI1) plays a key role in regulating the activity of Rho GTPases. However, the underlying mechanisms are still unclear. In this study, we show that protein phosphatase 1B (PPM1B) interacts with RhoGDI1 and functions as its phosphatase. Ectopic expression of PPM1B results in dephosphorylation of RhoGDI1 and, thereby, abates the activation of RhoA, Rac1 and CDC42 by epidermal growth factor (EGF). PPM1B overexpression in Hs578T and SKBR3 human breast cancer cells decreases their motility and invasiveness in vitro and cancer metastasis in vivo. In contrast, knockdown of PPM1B in MCF-7 and MDA-MB-468 human breast cancer cells that express endogenous PPM1B enhances EGF-induced RhoGDI1 phosphorylation, activation of Rho GTPases, and cancer cell migration and invasion. Knockdown of RhoA or Rac1 by siRNA reverses the enhanced cell migration seen after PP1MB depletion. Collectively, these results indicate that PPM1B negatively regulates cancer cell motility and invasiveness through dephosphorylating RhoGDI1.

Citations

Sep 8, 2019·Cells·Hee Jun ChoHee Gu Lee
May 13, 2020·Cancers·Haiyoung JungHee Gu Lee
Oct 14, 2020·Journal of Cellular and Molecular Medicine·Zhiyuan LuBaobing Zhao
Jul 11, 2020·Pharmacology & Therapeutics·Rui KamadaKazuyasu Sakaguchi
May 9, 2021·Cellular Signalling·Joachim NeumannUlrich Gergs
Jul 3, 2021·Cells·Rajakrishnan Veluthakal, Debbie C Thurmond
Apr 21, 2019·Biochemical and Biophysical Research Communications·Jong-Tae KimHee Gu Lee

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.