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An NFκB-dependent mechanism of tumor cell plasticity and lateral transmission of aggressive features

2018; Impact Journals LLC; Volume: 9; Issue: 42 Linguagem: Inglês

10.18632/oncotarget.25465

1949-2553

Nancy Adriana Espinoza‐Sánchez, Jennifer Enciso, Rosana Pelayo, Ezequiel M. Fuentes‐Pananá,

Cytokine Signaling Pathways and Interactions

// Nancy Adriana Espinoza-Sánchez 1, 5, * , Jennifer Enciso 2, 3, 4, * , Rosana Pelayo 4 and Ezequiel M. Fuentes-Pananá 5 1 Programa de Doctorado en Ciencias Biomédicas, Facultad de Medicina, Universidad Nacional Autónoma de México, C.P. 04510, Ciudad de México, México 2 Programa de Posgrado en Ciencias Bioquímicas, Universidad Nacional Autónoma de México, C.P. 04510, Ciudad de México, México 3 Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, C.P. 04510, Ciudad de México, México 4 Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, C.P. 74360, Metepec, Puebla, México 5 Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, C.P. 06720, Ciudad de México, México * These authors contributed equally to this work Correspondence to: Ezequiel M. Fuentes-Pananá, email: empanana@yahoo.com , Ezequiel.Fuentes@alumni.bcm.edu Keywords: Intra-tumor heterogeneity and intra-clonal communication; tumor aggression; cancer stem cells; invasion; NFκB and STAT signaling pathways Received: December 23, 2017 Accepted: May 07, 2018 Published: June 01, 2018 ABSTRACT Breast cancer is a complex disease exhibiting extensive inter- and intra-tumor heterogeneity. Inflammation is a well-known driver of cancer progression, often attributed to immune cells infiltrating the tumor stroma. However, tumor cells themselves are capable to secrete a variety of inflammatory molecules, of which we understand very little about their role in intra-clonal communication. We recently reported the capacity of triple negative cell lines to induce a cancer stem cell (CSC)-like phenotype and invasion properties into luminal cells, a mechanism mediated by pro-inflammatory cytokines that up-regulated the CXCL12/CXCR4/CXCR7 chemokine signaling axis. We performed transcriptional array analyses of CSCs-associated genes and cancer-inflammatory cell crosstalk genes and built regulatory networks with the data collected. We found a specific molecular signature segregating with the induced-invasive/stemness phenotype. Regulatory network analysis pointed out to an NFκB transcriptional signature, active in aggressive triple negative cells and in induced-invasive/CSC-like luminal cells. In agreement, NFκB inhibition abolished the induction of the stemness/invasive features. These data support an NFκB dependent mechanism of intra-clonal communication responsible for tumor cell plasticity leading the acquisition of cancer aggressive features. Understanding the communication between different tumor clones would help to find better therapeutic and prophylactic targets to prevent BrC progression and relapse.