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AGPAT9 suppresses cell growth,invasion and metastasis by counteracting acidic tumor microenvironment through KLF4/LASS2/V-ATPase signaling pathway in breast cancer
Authors:Shao-hua Fan  Yan-yan Wang  Zhi-yong Wu  Zi-feng Zhang  Jun Lu  Meng-qiu Li  Qun Shan  Dong-mei Wu  Chun-hui Sun  Bin Hu  Yuan-lin Zheng
Affiliation:1. Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, China;2. Department of Function Examination, The First People''s Hospital of Xuzhou, Jiangsu, China;3. Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
Abstract:
Human 1-acylglycerol-3-phosphate O-acyltransferase 9 (AGPAT9) is the gene identified from adipose tissue in 2007. We found AGPAT9 expression was significantly higher in poorly invasive MCF7 human breast cancer cells than the highly invasive MDA-MB-231 cells. AGPAT9 significantly inhibited the proliferation of breast cancer cells in vitro and in vivo. Live-cell imaging and transwell assays showed that AGPAT9 could significantly inhibit the migration and invasive capacities of breast cancer cells. The inhibitory effect of AGPAT9 on metastasis was also observed in vivo in lung metastasis model. AGPAT9 inhibited breast cancer cell proliferation, migration and invasion through, at least in part, suppressing the V-ATPase activity. In addition, increased AGPAT9 expression in MCF-7/ADR cells could increase the chemosensitivity to doxorubicin (Dox). Our findings suggest that increasing AGPAT9 expression may be a new approach that can be used for breast cancer treatment.
Keywords:breast cancer   AGPAT9   acidic tumor microenvironment   proliferation   invasion
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