Rab11b mediated integrin recycling promotes brain metastatic adaptation and outgrowth

ABSTRACT: Combining RNA sequencing of breast cancer brain metastases with reverse genetic screen in Drosophila melanogaster, we identified Rab11b, an endosomal recycling protein, as a mediator of metastatic adaptation. We show that disseminated cells up-regulate Rab11b early after arrival in the brain, allowing control of the cell surface proteome through recycling of proteins required for successful interaction with the microenvironment, including integrin B1. Rab11b-mediated control of integrin B1 surface expression allows ligation to the brain ECM, activating mechanotransduction signaling to allow survival and proliferation. We propose a model in which up-regulation of Rab11b allows disseminated cells to recycle needed proteins during metastatic adaptation, without strictly requiring transcription and translation, to allow for metastatic outgrowth.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Dr. Siyuan Zhang  

PROVIDER: MSV000085408 | MassIVE | Wed May 13 13:34:00 BST 2020

REPOSITORIES: MassIVE