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 (TGFβ2) was neutralized by TGFβ2 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 TGFβ2 and matrix metallopeptidase-3 (MMP-3) and suppressed the activation of p38. Conversely, overexpression of HOXA10 increased the levels of TGFβ2 and MMP-3. Further experiments identified that TGFβ2 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 TGFβ2-p38 MAPK pathway. Thus, HOXA10 could be a useful target for the treatment of pancreatic cancer.
BACKGROUND:HOXA10 is closely related to tumor progression in many humancancers. 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 (TGFβ2) was neutralized by TGFβ2 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 TGFβ2 and matrix metallopeptidase-3 (MMP-3) and suppressed the activation of p38. Conversely, overexpression of HOXA10 increased the levels of TGFβ2 and MMP-3. Further experiments identified that TGFβ2 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 TGFβ2-p38 MAPK pathway. Thus, HOXA10 could be a useful target for the treatment of pancreatic cancer.
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Authors: Young-Bem Se; Seung Hyun Kim; Ji Young Kim; Ja Eun Kim; Yun-Sik Dho; Jin Wook Kim; Yong Hwy Kim; Hyun Goo Woo; Se-Hyuk Kim; Shin-Hyuk Kang; Hak Jae Kim; Tae Min Kim; Soon-Tae Lee; Seung Hong Choi; Sung-Hye Park; Il Han Kim; Dong Gyu Kim; Chul-Kee Park Journal: Cancer Res Treat Date: 2016-07-19 Impact factor: 4.679