Rhophilin-associated tail protein 1 promotes migration and metastasis in triple negative breast cancer via activation of RhoA.

Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J Subsets: MEDLINE

Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley
Original Publication: [Bethesda, Md.] : The Federation, [c1987-

Cell Movement* ; Gene Expression Regulation, Neoplastic*; Adaptor Proteins, Signal Transducing/*metabolism ; Lung Neoplasms/*secondary ; Membrane Proteins/*metabolism ; Triple Negative Breast Neoplasms/*pathology ; rho GTP-Binding Proteins/*metabolism ; rhoA GTP-Binding Protein/*metabolism; Adaptor Proteins, Signal Transducing/genetics ; Animals ; Apoptosis ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Cell Proliferation ; Female ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Membrane Proteins/genetics ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness ; Prognosis ; Signal Transduction ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/metabolism ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; rho GTP-Binding Proteins/genetics ; rhoA GTP-Binding Protein/genetics

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with high motile and invasive capacity that contributes to metastasis. Understanding the mechanisms for the motility of TNBC might provide novel targetable vulnerabilities of the tumors. Herein, we find that Rhophilin-associated tail protein 1 (ROPN1) is selectively overexpressed in human TNBC cell lines and tissues. Overexpression of ROPN1 promotes, while silencing of ROPN1 inhibits the robust migration, invasion, and in vivo metastasis of TNBC cells. Moreover, we find that ROPN1 activates RhoA signaling via rhophilin-1 (RHPN1), leading to enhanced actin stress fibers formation in TNBC cells. RhoA signaling is demonstrated to be essential for ROPN1-mediated migration and metastasis of TNBC cells. Finally, we find that high levels of ROPN1 are significantly associated distant metastasis and predicted poor prognosis in patients with breast cancer. These findings reveal a novel mechanism for the high motility and metastasis of TNBC cells, suggesting that ROPN1 might be a potential prognostic marker and therapeutic target.
(© 2020 Federation of American Societies for Experimental Biology.)

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Keywords: ROPN1; RhoA; TNBC; actin stress fibers; metastasis

0 (Adaptor Proteins, Signal Transducing)
0 (Biomarkers, Tumor)
0 (Membrane Proteins)
0 (ROPN1 protein, human)
0 (rhophilin)
124671-05-2 (RHOA protein, human)
EC 3.6.5.2 (rho GTP-Binding Proteins)
EC 3.6.5.2 (rhoA GTP-Binding Protein)

Date Created: 20200520 Date Completed: 20210301 Latest Revision: 20210301

20221213

10.1096/fj.201903281R

32427399