Rab26 suppresses migration and invasion of breast cancer cells through mediating autophagic degradation of phosphorylated Src

Huiying Liu,Yang Han,Xiaoqing Liu,Hantian Qiu,Wanjin Hong,Yuxia Zhou,Ziyan Wang,Ran Tan,Tuanlao Wang,Ruijuan Zhuang,Xi Qiu,Liju Xu

doi:10.1038/s41419-021-03561-7

Abstract

Rab proteins play crucial roles in membrane trafficking. Some Rab proteins are implicated in cancer development through regulating protein sorting or degradation. In this study, we found that the expression of Rab26 is suppressed in the aggressive breast cancer cells as compared to the levels in non-invasive breast cancer cells. Over-expression of Rab26 inhibits cell migration and invasion, while Rab26 knockdown significantly promotes the migration and invasion of breast cancer cells. Rab26 reduces focal adhesion association of Src kinase and induces endosomal translocation of Src. Further experiments revealed that Rab26 mediates the autophagic degradation of phosphorylated Src through interacting with ATG16L1, consequently, resulting in the suppression of the migration and invasion ability of breast cancer cells.

Highlights

Cell adhesion, migration, and invasion are closely associated with the cancer development which are mediated by multiple types of proteins, including adhesion proteins, surface receptors, and their scaffolds
The aberrant internalization and recycling of integrin mediate the formation of focal adhesion to regulate migration and invasion of cancer cells[10,11], and the lysosomal degradation of surface protein such as E-cadherin enhances epithelial–mesenchymal transition (EMT)[12]
Since overexpression of Rab[26] reduced focal adhesion association of Src, we examined whether Rab[26] influences the level of phosphorylated Src

Summary

Introduction

Migration, and invasion are closely associated with the cancer development which are mediated by multiple types of proteins, including adhesion proteins, surface receptors, and their scaffolds. The aberrant internalization and recycling of integrin mediate the formation of focal adhesion to regulate migration and invasion of cancer cells[10,11], and the lysosomal degradation of surface protein such as E-cadherin enhances epithelial–mesenchymal transition (EMT)[12]. Dysregulated Rab proteins are implicated in multiple types of cancers by influencing the adhesion, motility, and invasion of cancer cells through regulating receptor endocytosis, recycling, or degradation[15,16]. Rab[5] plays a key role in the early stage of endocytosis, regulating the trafficking and signal transduction of multiple membrane receptors such as Official journal of the Cell Death Differentiation Association

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Conclusion