INPP4B suppresses HER2-induced mesenchymal transition in HER2+breast cancer and enhances sensitivity to Lapatinib
作者全名：Qu, Na; Wang, Gang; Su, Yue; Chen, Bo; Zhou, Duanfang; Wu, Yuanli; Yuan, Lie; Yin, Manjialan; Liu, Mingpu; Peng, Yang; Zhou, Weiying
作者地址：[Qu, Na; Wang, Gang; Su, Yue; Chen, Bo; Zhou, Duanfang; Wu, Yuanli; Yuan, Lie; Yin, Manjialan; Liu, Mingpu; Zhou, Weiying] Chongqing Med Univ, Coll Pharm, Dept Pharmacol, Chongqing 400016, Peoples R China; [Qu, Na; Wang, Gang; Su, Yue; Chen, Bo; Zhou, Duanfang; Wu, Yuanli; Yuan, Lie; Yin, Manjialan; Liu, Mingpu; Zhou, Weiying] Chongqing Med Univ, Chongqing Key Lab Drug Metab, Chongqing 400016, Peoples R China; [Qu, Na; Wang, Gang; Su, Yue; Chen, Bo; Zhou, Duanfang; Wu, Yuanli; Yuan, Lie; Yin, Manjialan; Liu, Mingpu; Zhou, Weiying] Chongqing Med Univ, Key Lab Biochem & Mol Pharmacol Chongqing, Chongqing 400016, Peoples R China; [Peng, Yang] Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrine Breast Surg, Chongqing 400016, Peoples R China
通信作者：Zhou, WY (通讯作者)，Chongqing Med Univ, Coll Pharm, Dept Pharmacol, Chongqing 400016, Peoples R China.; Peng, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrine Breast Surg, Chongqing 400016, Peoples R China.
来源：BIOCHEMICAL PHARMACOLOGY
ESI学科分类：PHARMACOLOGY & TOXICOLOGY
WOS号：WOS:001253300200001
JCR分区：Q1
影响因子：5.3
年份：2024
卷号：226
期号：
开始页：
结束页：
文献类型：Article
关键词：INPP4B; Breast cancer; HER2+; EMT; Lapatinib
摘要：Human epidermal growth factor receptor 2 positive (HER2+) breast cancer (BC) tends to metastasize and has a bad prognosis due to its high malignancy and rapid progression. Inositol polyphosphate 4-phosphatase isoenzymes type II (INPP4B) plays unequal roles in the development of various cancers. However, the function of INPP4B in HER2+ BC has not been elucidated. Here we found that INPP4B expression was significantly lower in HER2+ BC and positively correlated with the prognosis by bioinformatics and tissue immunofluorescence analyses. Overexpression of INPP4B inhibited cell proliferation, migration, and growth of xenografts in HER2+ BC cells. Conversely, depletion of INPP4B reversed these effects and activated the PDK1/AKT and Wnt/8-catenin signaling pathways to promote epithelial-mesenchymal transition (EMT) progression. Moreover, INPP4B overexpression blocked epidermal growth factor (EGF) -induced cell proliferation, migration and EMT progression, whereas INPP4B depletion antagonized HER2 depletion in reduction of cell proliferation and migration of HER2+ BC cells. Additionally, Lapatinib (LAP) inhibited HER2+ BC cell survival, proliferation and migration, and its effect was further enhanced by overexpression of INPP4B. In summary, our results illustrate that INPP4B suppresses HER2+ BC growth, migration and EMT, and its expression level affects patient outcome, further providing new insights into clinical practice.
基金机构：National Natural Science Foundation of China [82373901]; Chongqing Natural Science Foundation Innovation and Development Joint Fund [2022NSCQ-LZX0068]; Innovation research group in Colleges and Universities Program of Chongqing Municipal Education Commission [CXQT20012]; CQMU Program for Youth Innovation in Future Medicine [W0067]; Top Graduate Talent Cultivation Program of Chongqing Medical University [BJRC202218]
基金资助正文：This work was funded by the National Natural Science Foundation of China (No. 82373901) , Chongqing Natural Science Foundation Innovation and Development Joint Fund (2022NSCQ-LZX0068) , Innovation research group in Colleges and Universities Program of Chongqing Municipal Education Commission (No. CXQT20012) , CQMU Program for Youth Innovation in Future Medicine (W0067) and Top Graduate Talent Cultivation Program of Chongqing Medical University (BJRC202218) .
