Cargando…

Autophagy Inhibition Induces the Secretion of Macrophage Migration Inhibitory Factor (MIF) with Autocrine and Paracrine Effects on the Promotion of Malignancy in Breast Cancer

Breast cancer is the main cause of cancer-related death in women in the world. Because autophagy is a known survival pathway for cancer cells, its inhibition is currently being explored in clinical trials for treating several types of malignancies. In breast cancer, autophagy has been shown to be ne...

Descripción completa

Detalles Bibliográficos
Autores principales: Cotzomi-Ortega, Israel, Rosas-Cruz, Arely, Ramírez-Ramírez, Dalia, Reyes-Leyva, Julio, Rodriguez-Sosa, Miriam, Aguilar-Alonso, Patricia, Maycotte, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169388/
https://www.ncbi.nlm.nih.gov/pubmed/31963754
http://dx.doi.org/10.3390/biology9010020
_version_ 1783523778922283008
author Cotzomi-Ortega, Israel
Rosas-Cruz, Arely
Ramírez-Ramírez, Dalia
Reyes-Leyva, Julio
Rodriguez-Sosa, Miriam
Aguilar-Alonso, Patricia
Maycotte, Paola
author_facet Cotzomi-Ortega, Israel
Rosas-Cruz, Arely
Ramírez-Ramírez, Dalia
Reyes-Leyva, Julio
Rodriguez-Sosa, Miriam
Aguilar-Alonso, Patricia
Maycotte, Paola
author_sort Cotzomi-Ortega, Israel
collection PubMed
description Breast cancer is the main cause of cancer-related death in women in the world. Because autophagy is a known survival pathway for cancer cells, its inhibition is currently being explored in clinical trials for treating several types of malignancies. In breast cancer, autophagy has been shown to be necessary for the survival of cancer cells from the triple negative subtype (TNBC), which has the worst prognosis among breast cancers and currently has limited therapeutic options. Autophagy has also been involved in the regulation of protein secretion and, of importance for this work, the inhibition of autophagy is known to promote the secretion of proinflammatory cytokines from distinct cell types. We found that the inhibition of autophagy in TNBC cell lines induced the secretion of the macrophage migration inhibitory factor (MIF), a pro-tumorigenic cytokine involved in breast cancer invasion and immunomodulation. MIF secretion was dependent on an increase in reactive oxygen species (ROS) induced by the inhibition of autophagy. Importantly, MIF secreted from autophagy-deficient cells increased the migration of cells not treated with autophagy inhibitors, indicating that autophagy inhibition in cancer cells promoted malignancy in neighboring cells through the release of secreted factors, and that a combinatorial approach should be evaluated for cancer therapy.
format Online
Article
Text
id pubmed-7169388
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-71693882020-04-20 Autophagy Inhibition Induces the Secretion of Macrophage Migration Inhibitory Factor (MIF) with Autocrine and Paracrine Effects on the Promotion of Malignancy in Breast Cancer Cotzomi-Ortega, Israel Rosas-Cruz, Arely Ramírez-Ramírez, Dalia Reyes-Leyva, Julio Rodriguez-Sosa, Miriam Aguilar-Alonso, Patricia Maycotte, Paola Biology (Basel) Article Breast cancer is the main cause of cancer-related death in women in the world. Because autophagy is a known survival pathway for cancer cells, its inhibition is currently being explored in clinical trials for treating several types of malignancies. In breast cancer, autophagy has been shown to be necessary for the survival of cancer cells from the triple negative subtype (TNBC), which has the worst prognosis among breast cancers and currently has limited therapeutic options. Autophagy has also been involved in the regulation of protein secretion and, of importance for this work, the inhibition of autophagy is known to promote the secretion of proinflammatory cytokines from distinct cell types. We found that the inhibition of autophagy in TNBC cell lines induced the secretion of the macrophage migration inhibitory factor (MIF), a pro-tumorigenic cytokine involved in breast cancer invasion and immunomodulation. MIF secretion was dependent on an increase in reactive oxygen species (ROS) induced by the inhibition of autophagy. Importantly, MIF secreted from autophagy-deficient cells increased the migration of cells not treated with autophagy inhibitors, indicating that autophagy inhibition in cancer cells promoted malignancy in neighboring cells through the release of secreted factors, and that a combinatorial approach should be evaluated for cancer therapy. MDPI 2020-01-18 /pmc/articles/PMC7169388/ /pubmed/31963754 http://dx.doi.org/10.3390/biology9010020 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cotzomi-Ortega, Israel
Rosas-Cruz, Arely
Ramírez-Ramírez, Dalia
Reyes-Leyva, Julio
Rodriguez-Sosa, Miriam
Aguilar-Alonso, Patricia
Maycotte, Paola
Autophagy Inhibition Induces the Secretion of Macrophage Migration Inhibitory Factor (MIF) with Autocrine and Paracrine Effects on the Promotion of Malignancy in Breast Cancer
title Autophagy Inhibition Induces the Secretion of Macrophage Migration Inhibitory Factor (MIF) with Autocrine and Paracrine Effects on the Promotion of Malignancy in Breast Cancer
title_full Autophagy Inhibition Induces the Secretion of Macrophage Migration Inhibitory Factor (MIF) with Autocrine and Paracrine Effects on the Promotion of Malignancy in Breast Cancer
title_fullStr Autophagy Inhibition Induces the Secretion of Macrophage Migration Inhibitory Factor (MIF) with Autocrine and Paracrine Effects on the Promotion of Malignancy in Breast Cancer
title_full_unstemmed Autophagy Inhibition Induces the Secretion of Macrophage Migration Inhibitory Factor (MIF) with Autocrine and Paracrine Effects on the Promotion of Malignancy in Breast Cancer
title_short Autophagy Inhibition Induces the Secretion of Macrophage Migration Inhibitory Factor (MIF) with Autocrine and Paracrine Effects on the Promotion of Malignancy in Breast Cancer
title_sort autophagy inhibition induces the secretion of macrophage migration inhibitory factor (mif) with autocrine and paracrine effects on the promotion of malignancy in breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169388/
https://www.ncbi.nlm.nih.gov/pubmed/31963754
http://dx.doi.org/10.3390/biology9010020
work_keys_str_mv AT cotzomiortegaisrael autophagyinhibitioninducesthesecretionofmacrophagemigrationinhibitoryfactormifwithautocrineandparacrineeffectsonthepromotionofmalignancyinbreastcancer
AT rosascruzarely autophagyinhibitioninducesthesecretionofmacrophagemigrationinhibitoryfactormifwithautocrineandparacrineeffectsonthepromotionofmalignancyinbreastcancer
AT ramirezramirezdalia autophagyinhibitioninducesthesecretionofmacrophagemigrationinhibitoryfactormifwithautocrineandparacrineeffectsonthepromotionofmalignancyinbreastcancer
AT reyesleyvajulio autophagyinhibitioninducesthesecretionofmacrophagemigrationinhibitoryfactormifwithautocrineandparacrineeffectsonthepromotionofmalignancyinbreastcancer
AT rodriguezsosamiriam autophagyinhibitioninducesthesecretionofmacrophagemigrationinhibitoryfactormifwithautocrineandparacrineeffectsonthepromotionofmalignancyinbreastcancer
AT aguilaralonsopatricia autophagyinhibitioninducesthesecretionofmacrophagemigrationinhibitoryfactormifwithautocrineandparacrineeffectsonthepromotionofmalignancyinbreastcancer
AT maycottepaola autophagyinhibitioninducesthesecretionofmacrophagemigrationinhibitoryfactormifwithautocrineandparacrineeffectsonthepromotionofmalignancyinbreastcancer