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Blocking the Protein‐Protein Interaction between Gαh and PLCδ1 Inhibits Metastatic Progression in Triple‐Negative Breast Cancer
Author(s) -
Lin YuanFeng,
Liu PeiYao,
Hsiao Michael
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.600.15
Subject(s) - triple negative breast cancer , in vivo , cancer research , breast cancer , gene knockdown , metastatic breast cancer , in vitro , metastasis , cancer , biology , cell culture , medicine , biochemistry , genetics , microbiology and biotechnology
Breast cancer is thought to be a leading cause of poor survival rate in woman diseases. Especially triple‐negative breast cancer (TNBC) severely risks patient's life, usually owing to its metastatic progression. However, the molecular mechanism for cancer metastasis is still unclear in TNBC. Here find that Gαh which is originally identified as tissue transglutaminase acts as a poor prognostic marker in clinical cohort with breast cancer and exerts its G protein function to promote the invasiveness of TNBC cells in vitro and in vivo . Our data showed that the expression of Gαh causally associates with the in vitro invasion ability of TNBC cell lines. Moreover, the knockdown of Gαh obviously suppressed the in vitro invasion ability and the in vivo lung colonization capacity of highly metastatic TNBC cell lines MDA‐MB231 and HCC38 that express G α h protein abundantly. Conversely, the enforced expression of exogenous Gah markedly fostered the metastatic potentials in vitro and in vivo of TNBC cell lines MDA‐MB157 and HCC70 that express Gαh protein poorly. Certainly, the GTP‐binding activity, but not transamidating activity, of Gαh is crucial for promoting the metastatic evolution in TNBC cells. Furthermore, interrupting the protein‐protein interaction (PPI) of phospholipase C‐δ1 (PLCδ1) with Gαh by a synthetic peptide corresponding to PLCδ1 amino acid sequence TIPLNSLKQGYRHVHLM robustly suppressed the metastatic abilities of MDA‐MB231 cells in vitro and in vivo . These findings not only elucidate the critical role of Gαh/PLCδ1 signaling pathway in promoting the metastatic progression of TNBC but also provide a new strategy to combat TNBC metastasis via targeting the PPI of Gαh/PLCδ1 complex.