HOXA10 promotes cell invasion and MMP-3 expression via TGFβ2-mediated activation of the p38 MAPK pathway in pancreatic cancer cells.
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.
Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jing Wu Road, Jinan, 250021, China, cuixianp@163.com.
Xian-Ping
XP
Cui
Cheng-Kun
CK
Qin
Zhen-Hai
ZH
Zhang
Zhong-Xue
ZX
Su
Xin
X
Liu
Shi-Kang
SK
Wang
Xing-Song
XS
Tian
D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D055785:Gene Knockdown Techniques; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053781:Transforming Growth Factor beta2 / Q000378:metabolism*; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D014408:Biomarkers, Tumor; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D053781:Transforming Growth Factor beta2; C069634:HOXA10 protein, human; D048051:p38 Mitogen-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3