Myc as a Regulator of Ribosome Biogenesis and Cell Competition: A Link to Cancer

Abstract

The biogenesis of ribosomes is a finely regulated multistep process linked to cell proliferation and growth—processes which require a high rate of protein synthesis. One of the master regulators of ribosome biogenesis is Myc, a well-known proto-oncogene that has an important role in ribosomal function and in the regulation of protein synthesis. The relationship between Myc and the ribosomes was first highlighted in Drosophila, where Myc’s role in controlling Pol-I, II and III was evidenced by both microarrays data, and by the ability of Myc to control growth (mass), and cellular and animal size. Moreover, Myc can induce cell competition, a physiological mechanism through which cells with greater fitness grow better and thereby prevail over less competitive cells, which are actively eliminated by apoptosis. Myc-induced cell competition was shown to regulate both vertebrate development and tumor promotion; however, how these functions are linked to Myc’s control of ribosome biogenesis, protein synthesis and growth is not clear yet. In this review, we will discuss the major pathways that link Myc to ribosomal biogenesis, also in light of its function in cell competition, and how these mechanisms may reflect its role in favoring tumor promotion.

Dichotomous Impact of Myc on rRNA Gene Activation and Silencing in B Cell Lymphomagenesis

“…Myc is a key driver of ribosome biogenesis and protein synthesis, and thereby fuels sustained proliferative signaling and hypertrophy of nucleoli, i.e., two hallmarks of cancer [ 15 , 46 ]. The intimate link between Myc, ribosome biogenesis, and malignant transformation was imposingly demonstrated in the Eµ- Myc lymphoma model.…”

“…Intriguingly, Myc/Max heterodimers do not only act on RNA polymerase II (Pol II) transcribed genes, but also stimulates the synthesis of housekeeping non-coding RNAs, e.g., rRNA and tRNA, by Pol I and Pol III, respectively [ 11 , 12 , 13 , 14 ]. Thereby, they promote the concerted action of all three RNA polymerases required for ribosome biogenesis, and in turn stimulate protein synthesis and cell growth [ 15 ]. This mechanism is a rate-limiting determinant of cancer initiation, but is also required for the subsequent promotion and progression phases of carcinogenesis [ 4 , 16 ].…”

Pivotal Role of Fatty Acid Synthase in c-MYC Driven Hepatocarcinogenesis

“…The critical role of c-MYC in hepatocarcinogenesis has been proven undoubtedly by the finding that c-MYC overexpression suffices to trigger HCC development in mice [ 10 , 11 , 12 ]. It has been well established that c-MYC is a potent inducer of apoptosis [ 13 , 14 , 15 ]. This is a part of the normal defense mechanisms to eliminate cells which have potential to become cancer cells.…”

Single-cell sequencing of theDrosophilaembryonic heart and muscle cells during differentiation and maturation

“…The GO term analysis suggests that CBs increase the expression of genes necessary later for the translation of genes such as Mhc , Mlc2 and bent into muscle structural proteins during differentiation. This is also reflected by the anti-correlation of the expression of Myc and Mhc in CBs vs. CMs (Figure 3D): Myc is a master regulator of ribosome biogenesis and cell growth (Destefanis et al, 2020; Gallant, 2013; Grewal et al, 2005) and it is highly expressed prior to CM differentiation. We conclude that CBs during their final developmental steps of morphogenesis initiate a CM differentiation program, that enables robust expression (and translation) of sarcomeric genes, as well as other components necessary for contraction, such as ion channels (see below).…”