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

卷:9

Dalia Ramírez-Ramírez¹  Israel Cotzomi-Ortega¹  Arely Rosas-Cruz¹  Julio Reyes-Leyva¹  Paola Maycotte²  Patricia Aguilar-Alonso³  Miriam Rodriguez-Sosa⁴ 

[1] Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Km 4.5 Carretera Atlixco-Metepec HGZ5, Puebla 74360, Mexico;

[2] Consejo Nacional de Ciencia y Tecnología (CONACYT)—Centro de Investigación Biomédica de Oriente (CIBIOR), Instituto Mexicano del Seguro Social (IMSS), Puebla 74360, Mexico;

[3] Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, Puebla 72570, Mexico;

[4] Unidad de Biomedicina (UBIMED), Facultad de Estudios Superiores Iztacala (FES-I), Universidad Nacional Autónoma de México (UNAM), Tlanepantla 54090, Mexico;

关键词: autophagy;    mif;    breast cancer;    reactive oxygen species;    ros;    chloroquine;    secretion;    p115;   

DOI  :  10.3390/biology9010020

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown