MYC as a Multifaceted Regulator of Tumor Microenvironment Leading to Metastasis

Abstract

The Myc family of oncogenes is deregulated in many types of cancer, and their over-expression is often correlated with poor prognosis. The Myc family members are transcription factors that can coordinate the expression of thousands of genes. Among them, c-Myc (MYC) is the gene most strongly associated with cancer, and it is the focus of this review. It regulates the expression of genes involved in cell proliferation, growth, differentiation, self-renewal, survival, metabolism, protein synthesis, and apoptosis. More recently, novel studies have shown that MYC plays a role not only in tumor initiation and growth but also has a broader spectrum of functions in tumor progression. MYC contributes to angiogenesis, immune evasion, invasion, and migration, which all lead to distant metastasis. Moreover, MYC is able to promote tumor growth and aggressiveness by recruiting stromal and tumor-infiltrating cells. In this review, we will dissect all of these novel functions and their involvement in the crosstalk between tumor and host, which have demonstrated that MYC is undoubtedly the master regulator of the tumor microenvironment. In sum, a better understanding of MYC’s role in the tumor microenvironment and metastasis development is crucial in proposing novel and effective cancer treatment strategies.

PNSA, a Novel C-Terminal Inhibitor of HSP90, Reverses Epithelial–Mesenchymal Transition and Suppresses Metastasis of Breast Cancer Cells In Vitro

“…Besides, EMT-related proteins vimentin and MMP9 were up-regulated, and the proteolytic activity of MMP was enhanced in tumor metastasis [ 24 ]. Meanwhile, C-Myc, a transcription factor, is also increased, strongly contributing to invasion and migration [ 25 ]. As shown in Figure 3 D, PNSA induced a significant increase in E-cadherin expression and decreases in N-cadherin, vimentin, C-Myc, and MMP-9 expressions compared to DMSO group.…”

MicroRNA‑27b inhibits the development of melanoma by targeting MYC

“…miR-200c inhibits melanoma progression and drug resistance through downregulation of BMI-1 ( 37 ). According to the online expression profiles GSE77090, a total of 58 miRNAs are downregulated in melanoma (data not shown); among them, miR-27b may target MYC, which is a proto-oncogene ( 17 ). As previously reported, miR-27b suppresses the capacity of a number of cancer cell types to proliferate, invade and migrate.…”

“…The MYC gene is typically expressed constitutively in malignancies, and c-Myc, which is encoded by MYC, has been reported to regulate the gene expression of ≤15% of the human genome ( 16 ). From a clinical perspective, high expression levels of c-Myc protein exhibit a significant association with distant metastasis and impaired prognosis; from a biological perspective, the overexpression of c-Myc results in a significant increase in cell viability, invasion and migration ( 17 ). Furthermore, c-Myc increases the protein expression levels of Snail, which is an EMT marker, in vivo and in vitro ( 18 ).…”

Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics

“…The transcription factor C-Myc plays a key role in regulating cell proliferation, cell differentiation, and apoptosis [ 153 ]. Besides, it also supports tumor progression and metastasis [ 154 ]. The C-Myc was documented as a significant oncogene for pancreatic cancers and correlated with the perineural invasion [ 155 ].…”