Autophagy and Exosomes Relationship in Cancer: Friends or Foes?

Abstract

Autophagy is an intracellular degradation process involved in the removal of proteins and damaged organelles by the formation of a double-membrane vesicle named autophagosome and degraded through fusion with lysosomes. An intricate relationship between autophagy and the endosomal and exosomal pathways can occur at different stages with important implications for normal physiology and human diseases. Recent researches have revealed that extracellular vesicles (EVs), such as exosomes, could have a cytoprotective role by inducing intracellular autophagy; on the other hand, autophagy plays a crucial role in the biogenesis and degradation of exosomes. Although the importance of these processes in cancer is well established, their interplay in tumor is only beginning to be documented. In some tumor contexts (1) autophagy and exosome-mediated release are coordinately activated, sharing the molecular machinery and regulatory mechanisms; (2) cancer cell-released exosomes impact on autophagy in recipient cells through mechanisms yet to be determined; (3) exosome-autophagy relationship could affect drug resistance and tumor microenvironment (TME). In this review, we survey emerging discoveries relevant to the exosomes and autophagy crosstalk in the context of cancer initiation, progression and recurrence. Consequently, we discuss clinical implications by targeting autophagy-exosomal pathway interaction and how this could lay a basis for the purpose of novel cancer therapeutics.

MicroRNAs in Molecular Classification and Pathogenesis of Breast Tumors

“…A second inherent means of acquired resistance to targeted therapy trastuzumab (Tzb), actively deployed by Tzb-resistant (Tzb-R) HER2+ BC cells, is an upsurge in the rate of autophagy [ 83 ]. Autophagy is a cytoprotective mechanism adapted by both normal and tumor cells to increase cell survival during states of metabolic stress, hypoxia and chemotherapy-induced cell death [ 84 ]. The molecular mechanism that regulates autophagy is attributed to a tumor suppressor microRNA, miR-567, that is significantly downregulated in Tzb-R breast cancer [ 85 ].…”

Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

“… 104 In addition, exosome regulate drug resistance and tumor microenvironment in an autophagy-dependent manner. 105 For instance, exosomal circ-PVT1 promotes cisplatin resistance in gastric cancer cells by inducing cell autophagy and invasion and inhibiting apoptosis. 106 Furthermore, gastric cancer cell-derived exosomes trigger autophagy and promote activation of neutrophils, ultimately promoting gastric cancer cell migration.…”

Recent Advances in Understanding the Role of Autophagy in Paediatric Brain Tumours

“…The mechanisms by which this happens are certainly multifaceted and stimuli-dependent, with most of them remaining yet to be fully elucidated. Very recently, it has been proposed that exosome release within the tumour microenvironment (TME) can mediate autophagy-dependent therapy resistance [40]. Additionally, cancer stem cells (CSCs) are also known to be significantly involved in autophagy-mediated chemo-and immune-resistance, combining their already aggressive phenotype to autophagy activation, which further enhances tumour drug-resistance [41][42][43][44][45].…”