AGPAT9 suppresses cell growth, invasion and metastasis by counteracting acidic tumor microenvironment through KLF4/LASS2/V-ATPase signaling pathway in breast cancer.
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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AGPAT9 通过 KLF4/LASS2/V-ATPase 信号通路抵消乳腺癌中的酸性肿瘤微环境，从而抑制细胞生长、侵袭和转移。
DOI：
10.18632/oncotarget.4074
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发表时间：
2015-07-30
期刊：
影响因子：
--
通讯作者：
Zheng YL
中科院分区：
文献类型：
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作者：
Fan SH;Wang YY;Wu ZY;Zhang ZF;Lu J;Li MQ;Shan Q;Wu DM;Sun CH;Hu B;Zheng YL
人1-酰基甘油-3-磷酸O-酰基转移酶9(AGPAT9)是2007年从脂肪组织中发现的基因。我们发现AGPAT9在低侵袭性的MCF7人乳腺癌细胞中的表达明显高于高侵袭性的MDA-MB-231细胞。AGPAT9在体内外均能显著抑制乳腺癌细胞的增殖。活细胞成像和Transwell分析表明，AGPAT9能显著抑制乳腺癌细胞的迁移和侵袭能力。在肺转移模型中观察AGPAT9对肿瘤转移的抑制作用。AGPAT9至少部分通过抑制V-ATPase活性来抑制乳腺癌细胞的增殖、迁移和侵袭。此外，MCF-7/ADR细胞AGPAT9表达增加可增加对阿霉素(Dox)的化疗敏感性。我们的研究结果表明，增加AGPAT9的表达可能是一种新的治疗乳腺癌的方法。
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.