Secretory Autophagy Forges a Therapy Resistant Microenvironment in Melanoma
by
and
Silvina Odete Bustos
*, 
Nathalia Leal Santos
,
Roger Chammas
and
Luciana Nogueira de Sousa Andrade
* Center for Translational Research in Oncology (LIM24), Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo 01246-000, Brazil
*
Authors to whom correspondence should be addressed.
Cancers 2022, 14(1), 234; https://doi.org/10.3390/cancers14010234
Submission received: 30 October 2021
/
Revised: 22 December 2021
/
Accepted: 28 December 2021
/
Published: 4 January 2022
(This article belongs to the Special Issue Role of Autophagy in the Interactions between the Tumor and the Microenvironment)
Simple Summary
Tumor microenvironment (TME) is a complex of many cell types and extracellular matrix that play an active role in regulating and sustaining melanoma tumor progression. In this context, the secretion of several molecules, by secretory autophagy or exosome release, stimulates the intercellular communication between the different components of the TME modulating tumor response. Here, we discuss the current awareness around the role of extracellular secretion in melanoma TME and also investigate the molecules related to these secretion pathways in melanoma progression using public databases.
Abstract
Melanoma is the most aggressive skin cancer characterized by high mutational burden and large heterogeneity. Cancer cells are surrounded by a complex environment, critical to tumor establishment and progression. Thus, tumor-associated stromal components can sustain tumor demands or impair cancer cell progression. One way to manage such processes is through the regulation of autophagy, both in stromal and tumor cells. Autophagy is a catabolic mechanism that provides nutrients and energy, and it eliminates damaged organelles by degradation and recycling of cellular elements. Besides this primary function, autophagy plays multiple roles in the tumor microenvironment capable of affecting cell fate. Evidence demonstrates the existence of novel branches in the autophagy system related to cytoplasmic constituent’s secretion. Hence, autophagy-dependent secretion assembles a tangled network of signaling that potentially contributes to metabolism reprogramming, immune regulation, and tumor progression. Here, we summarize the current awareness regarding secretory autophagy and the intersection with exosome biogenesis and release in melanoma and their role in tumor resistance. In addition, we present and discuss data from public databases concerning autophagy and exosome-related genes as important mediators of melanoma behavior. Finally, we will present the main challenges in the field and strategies to translate most of the pre-clinical findings to clinical practice.
