Oncotarget

Research Papers:

Association of RAB5 overexpression in pancreatic cancer with cancer progression and poor prognosis via E-cadherin suppression

Takamichi Igarashi, Kenichiro Araki, Takehiko Yokobori, Bolag Altan, Takahiro Yamanaka, Norihiro Ishii, Mariko Tsukagoshi, Akira Watanabe, Norio Kubo, Tadashi Handa, Yasuo Hosouchi, Masahiko Nishiyama, Tetsunari Oyama, Ken Shirabe and Hiroyuki Kuwano _

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Oncotarget. 2017; 8:12290-12300. https://doi.org/10.18632/oncotarget.14703

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Abstract

Takamichi Igarashi1,2, Kenichiro Araki1,2, Takehiko Yokobori3, Bolag Altan2, Takahiro Yamanaka1,2, Norihiro Ishii1,2, Mariko Tsukagoshi1,2, Akira Watanabe1,2, Norio Kubo1,2, Tadashi Handa4, Yasuo Hosouchi5, Masahiko Nishiyama6, Tetsunari Oyama4, Ken Shirabe1,2,*, Hiroyuki Kuwano2,*

1Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

2Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gunma, Japan

3Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research, Maebashi, Gunma, Japan

4Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

5Department of Surgery and Laparoscopic Surgery, Gunma Prefecture Saiseikai-Maebashi Hospital, Maebashi, Gunma, Japan

6Department of Molecular Pharmacology and Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

*These authors have contributed equally to this work

Correspondence to:

Hiroyuki Kuwano, email: [email protected]

Keywords: RAB5, pancreatic cancer, epithelial mesenchymal transition, E-cadherin, cancer progression

Received: August 01, 2016    Accepted: December 27, 2016    Published: January 17, 2017

ABSTRACT

Pancreatic cancer is a common type of cancer with poor prognosis worldwide. Postoperative survival depends on the existence of metastasis. Elucidation of the mechanism underlying cancer progression is important to improve prognosis. The RAS-associated protein RAB5 activates intracellular membrane trafficking, and RAB5 expression is correlated to progression and epithelial mesenchymal transition in various cancers.

The expression of RAB5 and E-cadherin in 111 pancreatic cancer samples was investigated by immunohistochemical staining, and the relationship among RAB5 expression, clinicopathological factors, and E-cadherin expression was assessed. Furthermore, RAB5 suppression analysis by siRNA was performed to determine the roles of RAB5 in morphological change, proliferation potency, cell migration ability, and invasiveness of the pancreatic cancer cell line.

High RAB5 expression correlated with the presence of lymphatic invasion and venous invasion and low E-cadherin expression. Patients with high RAB5 expression had a poorer prognosis than those with low RAB5 expression. RAB5 suppression in pancreatic cancer cells enhanced E-cadherin expression; changed cell morphology from spindle to round; and inhibited proliferation, invasion, and cell migration.

RAB5 contributes to poor prognosis and progression in pancreatic cancer patients. It may be a promising candidate for individualized therapy in refractory pancreatic cancer.


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