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NCAPG confers trastuzumab resistance via activating SRC/STAT3 signaling pathway in HER2-positive breast cancer.


ABSTRACT: HER2+ breast cancer (BC) is characterized by rapid growth, early recurrence, early metastasis, and chemoresistance. Trastuzumab is the most effective treatment for HER2+ BC and effectively reduces the risk of recurrence and death of patients. Resistance to trastuzumab results in cancer recurrence and metastasis, leading to poor prognosis of HER2+ BC. In the present study, we found that non-structural maintenance of chromosome condensin 1 complex subunit G (NCAPG) expression was highly upregulated in trastuzumab-resistant HER2+ BC. Ectopic NCAPG was positively correlated with tumor relapse and shorter survival in HER2+ BC patients. Moreover, overexpression of NCAPG promoted, while silencing of NCAPG reduced, the proliferative and anti-apoptotic capacity of HER2+ BC cells both in vitro and in vivo, indicating NCAPG reduces the sensitivity of HER2+ BC cells to trastuzumab and may confer trastuzumab resistance. Furthermore, our results suggest that NCAPG triggers a series of biological cascades by phosphorylating SRC and enhancing nuclear localization and activation of STAT3. To summarize, our study explores a crucial role for NCAPG in trastuzumab resistance and its underlying mechanisms in HER2+ BC, and suggests that NCAPG could be both a potential prognostic marker as well as a therapeutic target to effectively overcome trastuzumab resistance.

SUBMITTER: Jiang L 

PROVIDER: S-EPMC7368860 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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NCAPG confers trastuzumab resistance via activating SRC/STAT3 signaling pathway in HER2-positive breast cancer.

Jiang Lili L   Ren Liangliang L   Chen Han H   Pan Jinyuan J   Zhang Zhuojun Z   Kuang Xiangqin X   Chen Xuhong X   Bao Wenhao W   Lin Chun C   Zhou Zhongqiu Z   Huang Danping D   Yang Jianan J   Huang Hongbiao H   Wang Lan L   Hou Ning N   Song Libing L  

Cell death & disease 20200718 7


HER2+ breast cancer (BC) is characterized by rapid growth, early recurrence, early metastasis, and chemoresistance. Trastuzumab is the most effective treatment for HER2+ BC and effectively reduces the risk of recurrence and death of patients. Resistance to trastuzumab results in cancer recurrence and metastasis, leading to poor prognosis of HER2+ BC. In the present study, we found that non-structural maintenance of chromosome condensin 1 complex subunit G (NCAPG) expression was highly upregulate  ...[more]

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