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CERS2 Suppresses Tumor Cell Invasion and is Associated with Decreased V‐ATPase and MMP‐2/MMP‐9 Activities in Breast Cancer
Author(s) -
Fan Shaohua,
Wang Yanyan,
Lu Jun,
Zheng Yuanlin,
Wu Dongmei,
Zhang Zifeng,
Shan Qun,
Hu Bin,
Li Mengqiu,
Cheng Wei
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24978
Subject(s) - matrix metalloproteinase , extracellular matrix , cancer research , chemistry , extracellular , gene knockdown , microbiology and biotechnology , biology , apoptosis , biochemistry
Ceramide synthase 2 ( CERS2 ) is the gene identified from a human liver cDNA library in 2001. Our previous studies have shown higher expression of CERS2 in the breast cancer patients was associated with fewer lymph node metastases. However, the molecular mechanism of CERS2 involved is unknown. Here, we found CERS2 was heterogeneously expressed in various breast cancer cells. The mRNA and protein expression levels of CERS2 in MCF7 cells, which are poorly invasive breast cancer cells, were obviously higher than that in the highly invasive cells MDA‐MB‐231. Results showed overexpression of CERS2 in MDA‐MB‐231 cells could significantly inhibit the migration and invasion ability, whereas CERS2 knockdown in MCF7 cells could significantly increase the migration and invasion ability. Overexpression of CERS2 in MDA‐MB‐231 cells significantly reduced the V‐ATPase activity, increased the extracellular pH and decreased the pH‐dependent activity of MMP‐2 and MMP‐9 matrix metalloproteinases (MMPs). CERS2 knockdown in MCF7 cells significantly increased the V‐ATPase activity, decreased the extracellular pH and increased the activity of MMP‐2 and MMP‐9. Taken together, CERS2 can significantly inhibit breast cancer cell invasion and is associated with the decrease of the V‐ATPase activity and extracellular hydrogen ion concentration, and in turn the activation of secreted MMP‐2/MMP‐9 and degradation of extracellular matrix (ECM), which ultimately suppressed tumor's invasion. Thus, CERS2 may represent a novel target for selectively disrupting V‐ATPase activity and the invasive potential of cancer cells. J. Cell. Biochem. 116: 502–513, 2015. © 2014 Wiley Periodicals, Inc.