c-MYC mediates the crosstalk between breast cancer cells and tumor microenvironment

Abstract

The MYC oncogenic family is dysregulated in diverse tumors which is generally linked to the poor prognosis of tumors. The members in MYC family are transcription factors which are responsible for the regulation of various genes expression. Among them, c-MYC is closely related to the progression of tumors. Furthermore, c-MYC aberrations is tightly associated with the prevalence of breast cancer. Tumor microenvironment (TME) is composed of many different types of cellular and non-cellular factors, mainly including cancer-associated fibroblasts, tumor-associated macrophages, vascular endothelial cells, myeloid-derived suppressor cells and immune cells, all of which can affect the diagnosis, prognosis, and therapeutic efficacy of breast cancer. Importantly, the biological processes occurred in TME, such as angiogenesis, immune evasion, invasion, migration, and the recruition of stromal and tumor-infiltrating cells are under the modulation of c-MYC. These findings indicated that c-MYC serves as a critical regulator of TME. Here, we aimed to summarize and review the relevant research, thus to clarify c-MYC is a key mediator between breast cancer cells and TME. Video Abstract.

Keywords: Breast cancer; Crosstalk; Tumor microenvironment; c-MYC.

Fig. 1

c-MYC is responsible for the crosstalk between breast cancer cells and tumor microenvironment. Within the tumor microenvironment, c-MYC can be regulated by several signaling proteins, such as STAT3, MAPK, β-catenin and mTOR. In addition, c-MYC contributes to the regulation of angiogenesis, the function of CAF and EMT. Moreover, c-MYC is able to modulate TAM, NK cell, T and B cell, as well as the expression of PD-L1 and CD47, thus leading to the immune evasion and immunosuppression. Besides, the tumor microenvironment can affect c-MYC expression in turn by various cytokines, the hypoxia microenvironment and the factors released from CAF