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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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Abstract

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.

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jing Wu Road, Jinan, 250021, China

    Xian-Ping Cui, Cheng-Kun Qin, Zhen-Hai Zhang, Zhong-Xue Su, Xin Liu & Shi-Kang Wang

  2. Department of Breast and Thyroid Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jing Wu Road, Jinan, 250021, China

    Xing-Song Tian

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  1. Xian-Ping Cui
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Cui, XP., Qin, CK., Zhang, ZH. et al. HOXA10 Promotes Cell Invasion and MMP-3 Expression Via TGFβ2-Mediated Activation of the p38 MAPK Pathway in Pancreatic Cancer Cells. Dig Dis Sci 59, 1442–1451 (2014). https://doi.org/10.1007/s10620-014-3033-6

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  • DOI: https://doi.org/10.1007/s10620-014-3033-6

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