國家衛生研究院 NHRI:Item 3990099045/9127

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Title:	MCT-1 expression promotes neoplastic multinucleation through the Src/p190B signaling activation in triple-negative breast cancer cells
Authors:	Wu, MH;Chen, YA;Chen, HH;Chang, KW;Chang, IS;Wang, LH;Hsu, HL
Contributors:	Institute of Molecular and Genomic Medicine;National Institute of Cancer Research
Abstract:	Multinucleation is associated with malignant neoplasm; however, the molecular mechanism underlying the nuclear abnormality remains unclear. Loss or mutation of PTEN is frequently implicated in the development of malignancies. We now demonstrate that increased expression of the oncogene MCT-1 antagonizes PTEN gene expression, protein stability and activation, thereby further promoting PI3K/AKT signaling and survival rate of the PTEN-deficient cells. MCT-1 interacts with p190B and Src in the triple negative breast cancer cells, supporting they are in proximity of the signaling complexes in vivo. MCT-1 overexpression and PTEN loss synergistically augmented the Src/p190B signaling function leading to inhibition of RhoA activity. Under such condition, the incidence of mitotic catastrophes including spindle multipolarity and cytokinesis failure were enhanced, driving a Src/p190B-dependent neoplastic multinucleation. Reduced MCT-1 expression by shRNA dramatically repressed the Src/p190B function and improved the nuclear structure, as well as suppressed tumorigenicity of the PTEN-null triple negative breast cancer cells. Consistent with the oncogenic effects in vitro, clinical evidence has confirmed that MCT-1 and p190B genes are highly expressed in human breast cancers. Accordingly, MCT-1 gene induction is recognized as a potentially indicator of breast tumor development. Abrogating MCT-1 function may be a promising strategy for treatment of the triple negative breast cancer involving aberrant activation of Src and/or dysfunction of PTEN.
Date:	2015-01
Relation:	Cancer Research. 2015 Jan;75(1, Suppl.):A69.
Link to:	http://dx.doi.org/10.1158/1538-7445.chtme14-a69
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000356630300050
Appears in Collections:	[Hsin-Ling Hsu] Conference Papers/Meeting Abstract [Lu-Hai Wang] Conference Papers/Meeting Abstract [I-Shou Chang] Conference Papers/Meeting Abstract

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