AGPAT9 suppresses cell growth, invasion and metastasis by counteracting acidic tumor microenvironment through KLF4/LASS2/V-ATPase signaling pathway in breast cancer
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Shao-hua Fan1,*, Yan-yan Wang2,*, Zhi-yong Wu3, Zi-feng Zhang1, Jun Lu1, Meng-qiu Li1, Qun Shan1, Dong-mei Wu1, Chun-hui Sun1, Bin Hu1, Yuan-lin Zheng1
1Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, China
2Department of Function Examination, The First People’s Hospital of Xuzhou, Jiangsu, China
3Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
*These authors have contributed equally to this work
Yuan-lin Zheng, e-mail: firstname.lastname@example.org
Keywords: breast cancer, AGPAT9, acidic tumor microenvironment, proliferation, invasion
Received: February 27, 2015 Accepted: June 08, 2015 Published: June 17, 2015
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.
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