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The Switch between Protective and Nonprotective Autophagy; Implications for Autophagy Inhibition as a Therapeutic Strategy in Cancer
Open AccessArticle

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

1
Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Km 4.5 Carretera Atlixco-Metepec HGZ5, Puebla 74360, Mexico
2
Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, Puebla 72570, Mexico
3
Unidad de Biomedicina (UBIMED), Facultad de Estudios Superiores Iztacala (FES-I), Universidad Nacional Autónoma de México (UNAM), Tlanepantla 54090, Mexico
4
Consejo Nacional de Ciencia y Tecnología (CONACYT)—Centro de Investigación Biomédica de Oriente (CIBIOR), Instituto Mexicano del Seguro Social (IMSS), Puebla 74360, Mexico
*
Author to whom correspondence should be addressed.
Biology 2020, 9(1), 20; https://doi.org/10.3390/biology9010020
Received: 27 November 2019 / Revised: 10 January 2020 / Accepted: 15 January 2020 / Published: 18 January 2020
(This article belongs to the Special Issue Autophagy in 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 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. View Full-Text
Keywords: autophagy; MIF; breast cancer; reactive oxygen species; ROS; chloroquine; secretion; p115 autophagy; MIF; breast cancer; reactive oxygen species; ROS; chloroquine; secretion; p115
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Cotzomi-Ortega, I.; Rosas-Cruz, A.; Ramírez-Ramírez, D.; Reyes-Leyva, J.; Rodriguez-Sosa, M.; Aguilar-Alonso, P.; Maycotte, P. Autophagy Inhibition Induces the Secretion of Macrophage Migration Inhibitory Factor (MIF) with Autocrine and Paracrine Effects on the Promotion of Malignancy in Breast Cancer. Biology 2020, 9, 20.

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