NDLI: Rab11a sustains GSK3β/Wnt/β-catenin signaling to enhance cancer progression in pancreatic cancer

Content Provider	Springer Nature Link
Author	Yu, Li Li, Xin Li, Haibin Chen, Huixin Liu, Hua
Copyright Year	2016
Abstract	The Rab family GTPases regulate many major biological processes during tumor progression such as cell proliferation, cytoskeleton organization, cell movement, and invasion. The present study aims to examine the clinical significance, biological roles, and molecular mechanism of Rab11a in pancreatic cancer progression. We examined expression pattern of Rab11a in 96 cases of pancreatic cancer specimens using immunohistochemistry and found Rab11a overexpression correlated with tumor-node-metastasis (TNM) stage (p = 0.0111). We depleted Rab11a in Bxpc3 cells using small interfering RNA (siRNA) and overexpressed Rab11a in Capan2 cells. Knockdown of Rab11a inhibited cell growth, invasion, and cell cycle progression while its overexpression facilitated cell growth, invasion, and cell cycle progression. In addition, Rab11a overexpression increased gemcitabine resistance and inhibited gemcitabine-induced apoptosis in Capan2 cells while its depletion reduced drug resistance. We investigated the role of Rab11a in the regulation of Wnt/β-catenin signaling and we demonstrated that Rab11a overexpression upregulated GSK3β phosphorylation and nuclear β-catenin accumulation. Rab11a depletion inhibited while its overexpression enhanced β-catenin/T-cell factor (TCF) transcriptional activity with corresponding change of Wnt target genes including cyclin D1, cyclin E, MMP7, and c-myc. Wnt inhibitor (FH535) partly attenuated the effects of Rab11a on cell proliferation and Wnt target genes. In conclusion, the present study demonstrated that Rab11a promotes aggressiveness of pancreatic cancer through GSK3β/Wnt/β-catenin signaling pathway.
Starting Page	13821
Ending Page	13829
Page Count	9
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	37
Issue Number	10
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-08-01
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Rab11a Pancreatic cancer Wnt Chemoresistance Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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