Autophagy and Extracellular Vesicles, Connected to rabGTPase Family, Support Aggressiveness in Cancer Stem Cells

Abstract

Even though cancers have been widely studied and real advances in therapeutic care have been made in the last few decades, relapses are still frequently observed, often due to therapeutic resistance. Cancer Stem Cells (CSCs) are, in part, responsible for this resistance. They are able to survive harsh conditions such as hypoxia or nutrient deprivation. Autophagy and Extracellular Vesicles (EVs) secretion are cellular processes that help CSC survival. Autophagy is a recycling process and EVs secretion is essential for cell-to-cell communication. Their roles in stemness maintenance have been well described. A common pathway involved in these processes is vesicular trafficking, and subsequently, regulation by Rab GTPases. In this review, we analyze the role played by Rab GTPases in stemness status, either directly or through their regulation of autophagy and EVs secretion.

Extracellular Vesicle Measurements with Nanoparticle Tracking Analysis: A Different Appreciation of Up and Down Secretion

“…Indeed, this protein is not the only one implicated in the EVs secretion. Several other RAB family members, the foremost being RAB27B, could endorse this role [4,5,15]. Therefore, we evaluated the expression of three RAB members mainly involved in EVs secretion: RAB27B, RAB35, and RAB11 (Figure 5).…”

“…Furthermore, considering that EVs secretion is a survival process for almost all tumoral cells, another explanation for not detecting EVs drop would be the implementation of another process to offset the loss of EVs. Indeed, other members of the RAB-GTPase family are able to endorse a function promoting EVs secretion instead of RAB27A [4,5,15]. When assessing the expression of RAB27B, RAB11 and RAB35, which may be the main potential actors of such a compensation, the only protein exhibiting an enhancement was RAB27B in the glioblastoma model.…”

“…When formed, these vesicles have to travel into the cell to be secreted. An important family of proteins involved in MVB trafficking is the RAB-GTPases family [1,4,5]. Several Rab proteins (5, 7, 11, and 35) mainly manage the intracellular movement along the microtubules, while RAB27A and RAB27B have been described to be crucial for exosome secretion.…”

Extracellular Vesicles in Triple–Negative Breast Cancer: Immune Regulation, Biomarkers, and Immunotherapeutic Potential

“…There are 10 members in the Rab GTPases family that facilitate the autophagic process, with the majority functioning at the autophagosome level [40]. The Rab GTPases maintain intracellular trafficking, regulating the traffic between organelles by recruiting effector proteins.…”