HOXA10 Promotes Cell Invasion and MMP-3 Expression Via TGFβ2-Mediated Activation of the p38 MAPK Pathway in Pancreatic Cancer Cells
HOXA10 Promotes Cell Invasion and MMP-3 Expression Via TGFβ2-Mediated Activation of the p38 MAPK Pathway in Pancreatic Cancer Cells
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DOI：
10.1007/s10620-014-3033-6
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发表时间：
2014-07-01
影响因子：
3.1
通讯作者：
Tian, Xing-Song
中科院分区：
文献类型：
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作者：
Cui, Xian-Ping;Qin, Cheng-Kun;Tian, Xing-Song
HOXA 10与许多人类癌症的肿瘤进展密切相关。然而，HOXA 10在胰腺癌中的作用仍不清楚。本研究旨在探讨HOXA 10在胰腺癌细胞侵袭和迁移中的作用，通过侵袭和迁移实验检测HOXA 10对胰腺癌细胞侵袭和迁移的影响。转化生长因子β 2（TGF β 2）的蛋白质被TGF β 2阻断抗体中和。SB 239063可抑制p38的活化，HOXA 10可促进胰腺癌细胞的侵袭和迁移。HOXA 10的敲低降低了TGF β 2和基质金属肽酶3（MMP-3）的表达，并抑制了p38的活化。相反，HOXA 10的过度表达增加了TGF β 2和MMP-3的水平。进一步的实验表明，TGF β 2参与HOXA 10促进的侵袭和迁移，并调节MMP-3表达和p38激活。抑制p38可抑制胰腺癌细胞的侵袭和MMP-3的表达，HOXA 10可通过TGF β 2-p38 MAPK途径促进胰腺癌细胞的侵袭和MMP-3的表达。因此，HOXA 10可能是治疗胰腺癌的有用靶点。
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.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.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.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.