Rab23 promotes squamous cell carcinoma cell migration and invasion via integrin β1/Rac1 pathway
نویسندگان
چکیده
Rab23 was a member of Ras-related small GTPase family, which played a key role in the regulation of Shh signaling pathway. However, the function and regulatory mechanism of Rab23 in cutaneous squamous cell carcinoma was unknown. In this study, we found that the expression level of Rab23 was higher in moderately to poorly tumor differentiation tissue and non-exposed positions, and no statistically significant difference showed in Rab23 expression according to trauma/chronic disease, location on lips/ears, tumor size, gender, or age. Interestingly, we found that Rab23 RNAi suppressed cell invasion and Rab23 overexpression promoted cell invasion depended on GTP-bound form of Rab23. Inhibition of Rac1 activity or Rac1 silencing with siRNA fragment attenuated Rab23 promoted cells migration and invasion. Notably, we confirmed that Rab23 was co-localized with integrin β1 in cell membrane of Rab23 WT and Rab23 Q68L stable expression cells and Rab23 efficiently coprecipitated with integrin β1 and Tiam1 in a GTP-dependent manner. Further, integrin β1 siRNA interrupted the coprecipitation between Rab23 and Tiam1 and attenuated Rab23 promoted cells migration and invasion. Taken together, our results indicated that Rab23 promotes squamous cell carcinoma cells migration and invasion by regulating Integrin β1/Tiam1/Rac1 pathway.
منابع مشابه
Pro‐migratory and TGF‐β‐activating functions of αvβ6 integrin in pancreatic cancer are differentially regulated via an Eps8‐dependent GTPase switch
The integrin αvβ6 is up-regulated in numerous carcinomas, where expression commonly correlates with poor prognosis. αvβ6 promotes tumour invasion, partly through regulation of proteases and cell migration, and is also the principal mechanism by which epithelial cells activate TGF-β1; this latter function complicates therapeutic targeting of αvβ6, since TGF-β1 has both tumour-promoting and -supp...
متن کاملLoss of miR-200b promotes invasion via activating the Kindlin-2/integrin β1/AKT pathway in esophageal squamous cell carcinoma: An E-cadherin-independent mechanism
Our previous studies have shown that loss of miR-200b enhances the invasiveness of esophageal squamous cell carcinoma (ESCC) cells. However, whether the miR-200-ZEB1/2-E-cadherin regulatory cascade, a master regulator of epithelial-to-mesenchymal transition (EMT), is involved in the regulation of ESCC invasion remains elusive. Here, we show that miR-200b represses ESCC cell invasion in vivo wit...
متن کاملIntegrin β1 is a critical effector in promoting metastasis and chemo-resistance of esophageal squamous cell carcinoma.
Metastasis of esophageal squamous cell carcinoma (ESCC) remains a challenge in clinical practice. In this study, we clarified that integrin β1 (ITGB1) plays critical roles in the metastasis of ESCC. By analyzing the expression of integrin β1 in ESCC specimens, we found that the expression of this integrin was higher in malignant than in normal tissues and that this increase was associated with ...
متن کاملTransmembrane Collagen XVII Modulates Integrin Dependent Keratinocyte Migration via PI3K/Rac1 Signaling
The hemidesmosomal transmembrane component collagen XVII (ColXVII) plays an important role in the anchorage of the epidermis to the underlying basement membrane. However, this adhesion protein seems to be also involved in the regulation of keratinocyte migration, since its expression in these cells is strongly elevated during reepithelialization of acute wounds and in the invasive front of squa...
متن کاملThe Diacylglycerol Kinase α/Atypical PKC/β1 Integrin Pathway in SDF-1α Mammary Carcinoma Invasiveness
Diacylglycerol kinase α (DGKα), by phosphorylating diacylglycerol into phosphatidic acid, provides a key signal driving cell migration and matrix invasion. We previously demonstrated that in epithelial cells activation of DGKα activity promotes cytoskeletal remodeling and matrix invasion by recruiting atypical PKC at ruffling sites and by promoting RCP-mediated recycling of α5β1 integrin to the...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 7 شماره
صفحات -
تاریخ انتشار 2016