An NFκB-dependent mechanism of tumor cell plasticity and lateral transmission of aggressive features
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Nancy Adriana Espinoza-Sánchez1,5,*, Jennifer Enciso2,3,4,*, Rosana Pelayo4 and Ezequiel M. Fuentes-Pananá5
1Programa de Doctorado en Ciencias Biomédicas, Facultad de Medicina, Universidad Nacional Autónoma de México, C.P. 04510, Ciudad de México, México
2Programa de Posgrado en Ciencias Bioquímicas, Universidad Nacional Autónoma de México, C.P. 04510, Ciudad de México, México
3Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, C.P. 04510, Ciudad de México, México
4Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, C.P. 74360, Metepec, Puebla, México
5Unidad 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
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
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.
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