MYC, Cell Competition, and Cell Death in Cancer: The Inseparable Triad

Abstract

Deregulation of MYC family proteins in cancer is associated with a global reprogramming of gene expression, ultimately promoting glycolytic pathways, cell growth, and proliferation. It is well known that MYC upregulation triggers cell-autonomous apoptosis in normal tissues, while frankly malignant cells develop resistance to apoptotic stimuli, partly resulting from MYC addiction. As well as inducing cell-autonomous apoptosis, MYC upregulation is able to trigger non cell-autonomous apoptotic death through an evolutionarily conserved mechanism known as “cell competition”. With regard to this intimate and dual relationship between MYC and cell death, recent evidence obtained in Drosophila models of cancer has revealed that, in early tumourigenesis, MYC upregulation guides the clonal expansion of mutant cells, while the surrounding tissue undergoes non-cell autonomous death. Apoptosis inhibition in this context was shown to restrain tumour growth and to restore a wild-type phenotype. This suggests that cell-autonomous and non cell-autonomous apoptosis dependent on MYC upregulation may shape tumour growth in different ways, soliciting the need to reconsider the role of cell death in cancer in the light of this new level of complexity. Here we review recent literature about MYC and cell competition obtained in Drosophila, with a particular emphasis on the relevance of cell death to cell competition and, more generally, to cancer. Possible implications of these findings for the understanding of mammalian cancers are also discussed.

Targeting Wnt/β‐catenin and PI3K/Akt/mTOR pathways in T‐cell acute lymphoblastic leukemia

“…First, we analyzed the expression of two canonical Wnt/β‐catenin target genes, involved in cancer cell proliferation and survival that are activated by nuclear translocation of β‐catenin: C‐MYC and BIRC5. BIRC5 encodes the protein survivin (Di Giacomo, Sollazzo, Paglia, & Grifoni, ; Verdecia et al, ). We treated T‐ALL cell lines for 24 hr with ICG‐001, ZSTK‐474, or the combination of the two drugs and we evaluated the expression of the two genes by qRT‐PCR.…”

“…Taken together, our findings demonstrated that ICG-001 and ZSTK-474 have cytostatic effects when administrated separately while they induce apoptosis when administrated together.3.2 | Wnt/β-catenin and PI3K/Akt/mTOR signaling pathway are modulated by ICG-001 and ZSTK-474To understand how ICG-001 and ZSTK-474 act at the molecular level, we analyzed the expression of some components of Wnt/β-catenin(Figure 3a,b) and PI3K/Akt signaling at the transcript and/or protein level.First, we analyzed the expression of two canonical Wnt/β-catenin target genes, involved in cancer cell proliferation and survival that are activated by nuclear translocation of β-catenin: C-MYC and BIRC5. BIRC5 encodes the protein survivin (DiGiacomo, Sollazzo, Paglia, & Grifoni, 2017;Verdecia et al, 2000). We treated T-ALL cell lines for 24 hr with ICG-001, ZSTK-474, or the combination of the…”

circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signaling

“…The abnormal activation of this pathway initiates the expression disorder of downstream target genes such as c-Myc and cyclin D1. c-Myc protein has the dual function of stimulating cell proliferation and regulating apoptosis (Ciribilli et al 2015;Di Giacomo et al 2017). Increased β-catenin in cytoplasm activates cyclin D1 which is key regulators of cell cycle promoting cell division, leading to uncontrolled cell proliferation and carcinogenesis (Mo et al 2019).…”

Integrated Molecular Characterisation of the MAPK Pathways in Human Cancers

“…Recent studies show that, in malignant cells, the expression of the MYC oncogene is crucial for cancer cells to colonise organs at the expense of less performant neighbours. As a consequence of this, a functional MYC gene is necessary for the survival and clonal expansion of tumorous masses [36][37][38] .…”