Carbonic anhydrase XII promotes invasion and migration ability of MDA-MB-231 breast cancer cells through the p38 MAPK signaling pathway.
Carbonic anhydrase (CA) XII, an extracellular enzyme involved in the regulation of the microenvironment acidity and tumor malignant phenotype, was originally identified as a protein overexpressed in some types of cancers, including breast cancer. However, the cellular function and mechanism of CAXII remained unclear. In this study, the effects of CAXII expression on invasion and migration of breast cancer cells was investigated. Gene knockdown of CAXII in the human breast cancer cell line MDA-MB-231 resulted in decreased invasion and migration by interfering with the p38 MAPK pathway. CAXII knockdown also decreased the expression of matrix metalloproteinase (MMP)-2, MMP-9, and urokinase-type plasminogen activator (u-PA), but increased tissue inhibitor of metalloproteinases (TIMP)-2 and plasminogen activator inhibitor (PAI)-1 expression. Furthermore, decreased invasive and migration ability of CAXII-knockdown cells were restored by an overexpression of CAXII. Results also showed that CAXII knockdown may decrease anchorage-independent growth and cell growth by inhibiting CDK6 and cyclin D1 expression. Furthermore, the impact of CAXII knockdown on invasion, migration and cell growth was further evidenced by effects on tumor size and metastasis of MDA-MB-231 cells in vivo. Taken together, these data suggested that CAXII may affect the capability of invasion and migration of MDA-MB-231 cells, which may be mediated through the p38 MAPK pathway.
Hsieh
Ming-Ju
MJ
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, ROC.
Chen
Kuo-Shuen
KS
Chiou
Hui-Ling
HL
Hsieh
Yih-Shou
YS
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002256:Carbonic Anhydrases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D020868:Gene Silencing; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D055293:Receptors, Urokinase Plasminogen Activator; D019716:Tissue Inhibitor of Metalloproteinase-2; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; C483903:CA13 protein, human; D002256:Carbonic Anhydrases