PMID- 24464212 OWN - NLM STAT- MEDLINE DCOM- 20140826 LR - 20220409 IS - 1573-2568 (Electronic) IS - 0163-2116 (Linking) VI - 59 IP - 7 DP - 2014 Jul TI - HOXA10 promotes cell invasion and MMP-3 expression via TGFbeta2-mediated activation of the p38 MAPK pathway in pancreatic cancer cells. PG - 1442-51 LID - 10.1007/s10620-014-3033-6 [doi] AB - BACKGROUND: HOXA10 is closely related to tumor progression in many human cancers. However, the role of HOXA10 in pancreatic cancer remains unclear. The aim of this study was to determine the involvement of HOXA10 in pancreatic cancer cell invasion and migration. METHODS: The effect of HOXA10 on the invasion and migration of pancreatic cancer cells was assessed by invasion and migration assays. The protein of transforming growth factor beta-2 (TGFbeta2) was neutralized by TGFbeta2 blocking antibody. The activation of p38 was inhibited by SB239063. RESULTS: HOXA10 could promote the invasion and migration of pancreatic cancer cells. Knockdown of HOXA10 decreased the expressions of TGFbeta2 and matrix metallopeptidase-3 (MMP-3) and suppressed the activation of p38. Conversely, overexpression of HOXA10 increased the levels of TGFbeta2 and MMP-3. Further experiments identified that TGFbeta2 contributed to the HOXA10-promoted invasion and migration and regulated MMP-3 expression and p38 activation. Additionally, inhibition of p38 suppressed cell invasion and MMP-3 expression in pancreatic cancer cells. CONCLUSIONS: HOXA10 promotes cell invasion and MMP-3 expression of pancreatic cancer cells via TGFbeta2-p38 MAPK pathway. Thus, HOXA10 could be a useful target for the treatment of pancreatic cancer. FAU - Cui, Xian-Ping AU - Cui XP AD - Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jing Wu Road, Jinan, 250021, China, cuixianp@163.com. FAU - Qin, Cheng-Kun AU - Qin CK FAU - Zhang, Zhen-Hai AU - Zhang ZH FAU - Su, Zhong-Xue AU - Su ZX FAU - Liu, Xin AU - Liu X FAU - Wang, Shi-Kang AU - Wang SK FAU - Tian, Xing-Song AU - Tian XS LA - eng PT - Journal Article DEP - 20140125 PL - United States TA - Dig Dis Sci JT - Digestive diseases and sciences JID - 7902782 RN - 0 (Biomarkers, Tumor) RN - 0 (Homeobox A10 Proteins) RN - 0 (Homeodomain Proteins) RN - 0 (Transforming Growth Factor beta2) RN - 140441-81-2 (HOXA10 protein, human) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Biomarkers, Tumor/*metabolism MH - Blotting, Western MH - Cell Line, Tumor MH - Cell Movement/*physiology MH - Enzyme-Linked Immunosorbent Assay MH - Gene Knockdown Techniques MH - Homeobox A10 Proteins MH - Homeodomain Proteins/*metabolism MH - Humans MH - Matrix Metalloproteinase 3/*metabolism MH - Neoplasm Invasiveness MH - Pancreatic Neoplasms/metabolism/pathology/*physiopathology MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transforming Growth Factor beta2/*metabolism MH - Up-Regulation MH - p38 Mitogen-Activated Protein Kinases/*metabolism EDAT- 2014/01/28 06:00 MHDA- 2014/08/27 06:00 CRDT- 2014/01/28 06:00 PHST- 2013/08/18 00:00 [received] PHST- 2014/01/08 00:00 [accepted] PHST- 2014/01/28 06:00 [entrez] PHST- 2014/01/28 06:00 [pubmed] PHST- 2014/08/27 06:00 [medline] AID - 10.1007/s10620-014-3033-6 [doi] PST - ppublish SO - Dig Dis Sci. 2014 Jul;59(7):1442-51. doi: 10.1007/s10620-014-3033-6. Epub 2014 Jan 25.