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Targeting the Protein‐Protein Interaction between Gαh and PLCδ1 Prevents Metastatic Progression in Triple‐Negative Breast Cancer
Author(s) -
Lin YuanFeng,
Huang ShangPen,
Chen ChiLong
Publication year - 2017
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.31.1_supplement.lb498
Subject(s) - triple negative breast cancer , breast cancer , cancer research , metastatic breast cancer , medicine , metastasis , cancer , lymph node , ca15 3 , oncology
The distant metastasis of triple‐negative breast cancer (TNBC) to other organs, e.g. lung, has been correlated with poor survival rates in breast cancer patients. Therefore, the identification of useful drug‐targets to prevent metastasis or even inhibit tumor growth of TNBC is urgently needed. Here we showed that the increased level of cytosol, not extracellular, Gah is a poor prognostic marker in breast cancer patients and correlates with the metastatic evolution in TNBC cells. Moreover, the G protein, not transamidating, activity of Gαh was appeared to be critical for promoting the metastatic potentials of TNBC cells. We further showed that the protein‐protein interaction (PPI) between Gαh and PLCδ1 plays a pivotal role in regulating cellular invasion ability of TNBC cells and the signature of combining high Gαh/PLCδ1 levels refers to a worse prognosis in clinical patients with breast cancer and correlates with lymph node metastasis of ER(−) breast cancer. Our data revealed that blocking the PPI of Gαh/PLCδ1 complex by the synthetically myristoylated PLCδ1 peptide corresponding to the Gαh‐binding interface appears to significantly suppress cellular invasiveness in vitr o and inhibit in vivo lung‐metastatic colonies of TNBC cells. This report establishes Gαh/PLCδ1 as a poor prognosis factor in breast cancer patients and provides a therapeutic value of targeting the PPI of Gαh/PLCδ1 complex for combating the metastatic progression of TNBCs. Support or Funding Information This study was supported Ministry of Science and Technology (MOST 104‐2320‐B‐038‐061‐MY3) and Taipei Medical University (TMU103‐AE1‐B13) to Dr. Yuan‐Feng Lin.