HOXA10 Promotes Cell Invasion and MMP-3 Expression Via TGF[beta]2-Mediated Activation of the p38 MAPK Pathway in Pancreatic Cancer Cells

• Published in: Digestive diseases and sciences Vol. 59; no. 7; p. 1442
• Main Authors: Cui, Xian-Ping, Qin, Cheng-Kun, Zhang, Zhen-Hai, Su, Zhong-Xue, Liu, Xin, Wang, Shi-Kang, Tian, Xing-Song
• Format: Journal Article
• Language: English
• Published: New York Springer 01.07.2014; Springer Nature B.V
• Subjects: Antibodies; Cancer cells; Development and progression; Pancreatic cancer; Transforming growth factors; Viral antibodies
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-014-3033-6

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 (TGF[beta]2) was neutralized by TGF[beta]2 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 TGF[beta]2 and matrix metallopeptidase-3 (MMP-3) and suppressed the activation of p38. Conversely, overexpression of HOXA10 increased the levels of TGF[beta]2 and MMP-3. Further experiments identified that TGF[beta]2 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 TGF[beta]2-p38 MAPK pathway. Thus, HOXA10 could be a useful target for the treatment of pancreatic cancer.