Igarashi Takamichi, Araki Kenichiro, Yokobori Takehiko, Altan Bolag, Yamanaka Takahiro, Ishii Norihiro, Tsukagoshi Mariko, Watanabe Akira, Kubo Norio, Handa Tadashi, Hosouchi Yasuo, Nishiyama Masahiko, Oyama Tetsunari, Shirabe Ken, Kuwano Hiroyuki
Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gunma, Japan.
Oncotarget. 2017 Feb 14;8(7):12290-12300. doi: 10.18632/oncotarget.14703.
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.
胰腺癌是一种全球范围内预后较差的常见癌症类型。术后生存率取决于是否存在转移。阐明癌症进展的潜在机制对于改善预后很重要。RAS相关蛋白RAB5激活细胞内膜运输，并且RAB5的表达与多种癌症的进展和上皮间质转化相关。通过免疫组织化学染色研究了111例胰腺癌样本中RAB5和E-钙黏蛋白的表达，并评估了RAB5表达、临床病理因素和E-钙黏蛋白表达之间的关系。此外，通过小干扰RNA（siRNA）进行RAB5抑制分析，以确定RAB5在胰腺癌细胞系的形态变化、增殖能力、细胞迁移能力和侵袭性中的作用。RAB5高表达与淋巴浸润和静脉浸润的存在以及E-钙黏蛋白低表达相关。RAB5高表达的患者比RAB5低表达的患者预后更差。胰腺癌细胞中RAB5的抑制增强了E-钙黏蛋白的表达；将细胞形态从纺锤形变为圆形；并抑制了增殖、侵袭和细胞迁移。RAB5导致胰腺癌患者预后不良和病情进展。它可能是难治性胰腺癌个体化治疗的一个有前景的候选者。
