Expression of Rab5a correlates with tumor progression in pancreatic carcinoma.

Abstract

Rab family protein Rab5a has been implicated in cancer progression. To date, its expression pattern in human pancreatic cancer has not been investigated. This study aims to examine clinical significance, biological role, and potential mechanism of action of mRab5a in human pancreatic cancer. We analyzed Rab5a protein in cancer tissue of 111 cases of pancreatic cancer using immunohistochemistry. The results show that Rab5a overexpression correlates with high T stage, positive nodal status, and advanced TNM stage. We performed knockdown of Rab5a through transfection of Rab5a-specific siRNA in the Capan-2 cell line, which shows high endogenous expression, and of Rab5a plasmid in the CFPAC-1 cell line, which shows low endogenous expression. Rab5a knockdown inhibited cell proliferation and invasion while its overexpression promoted cell proliferation and invasion. In addition, overexpression of Rab5a induced resistance to 5-FU and gemcitabine while its knockdown reduced resistance to 5-FU and gemcitabine. Furthermore, our results show that Rab5a overexpression upregulates Wnt signaling and expression of Wnt target genes including c-myc and MMP7. Blocking Wnt signaling abolished the effects of Rab5a on Wnt targets and on cancer cell proliferation. In summary, our results show that Rab5a is overexpressed in pancreatic cancer and promotes aggressive biological behavior through regulation of the Wnt/β-catenin signaling pathway.

• Authors: Yuandong Li, Xiaofang Sun, Donghui Ji, Xiangshun Kong, Dengxiang Liu, Zhenya Zhao, Jingbo Yan, Shubo Chen
• Journal: Virchows Archiv : an international journal of pathology (Virchows Arch) Vol. 470 Issue 5 Pg. 527-536 (May 2017) ISSN: 1432-2307 [Electronic] Germany
• PMID: 28243729 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• RAB5C protein, human
• rab5 GTP-Binding Proteins

Topics

• Biomarkers, Tumor (analysis)
• Blotting, Western
• Carcinoma, Pancreatic Ductal (pathology)
• Disease Progression
• Gene Knockdown Techniques
• Humans
• Immunohistochemistry
• Pancreatic Neoplasms (pathology)
• Prognosis
• Real-Time Polymerase Chain Reaction
• Wnt Signaling Pathway (physiology)
• rab5 GTP-Binding Proteins (analysis, biosynthesis)