MYC: there is more to it than cancer

Abstract

MYC is a pleiotropic transcription factor involved in multiple cellular processes. While its mechanism of action and targets are not completely elucidated, it has a fundamental role in cellular proliferation, differentiation, metabolism, ribogenesis, and bone and vascular development. Over 4 decades of research and some 10,000 publications linking it to tumorigenesis (by searching PubMed for “MYC oncogene”) have led to MYC becoming a most-wanted target for the treatment of cancer, where many of MYC’s physiological functions become co-opted for tumour initiation and maintenance. In this context, an abundance of reviews describes strategies for potentially targeting MYC in the oncology field. However, its multiple roles in different aspects of cellular biology suggest that it may also play a role in many additional diseases, and other publications are indeed linking MYC to pathologies beyond cancer. Here, we review these physiological functions and the current literature linking MYC to non-oncological diseases. The intense efforts towards developing MYC inhibitors as a cancer therapy will potentially have huge implications for the treatment of other diseases. In addition, with a complementary approach, we discuss some diseases and conditions where MYC appears to play a protective role and hence its increased expression or activation could be therapeutic.

Endothelial c-Myc knockout disrupts metabolic homeostasis and triggers the development of obesity

“…Outside the domain of cancer, c-Myc plays a significant physiological and pathological role ( Rosselot et al, 2021 ; Nevzorova and Cubero, 2023 ; Prochownik and Wang, 2023 ; Zacarias-Fluck et al, 2024 ). Although therapeutic interventions involving direct c-Myc manipulation may present challenges, the protective effects observed across various parameters suggest that its targeting may offer an approach to mitigate obesity-associated complications.…”

“…The transcription factor c-Myc plays an important physiological role controlling multiple cellular functions ( Hofmann et al, 2015 ; Zacarias-Fluck et al, 2024 ). Deregulated c-Myc expression has been associated with cancer, metabolic and inflammatory conditions ( Zheng et al, 2017 ; Luo et al, 2021 ; Rosselot et al, 2021 ; Nevzorova and Cubero, 2023 ; Zacarias-Fluck et al, 2024 ).…”

“…The transcription factor c-Myc plays an important physiological role controlling multiple cellular functions ( Hofmann et al, 2015 ; Zacarias-Fluck et al, 2024 ). Deregulated c-Myc expression has been associated with cancer, metabolic and inflammatory conditions ( Zheng et al, 2017 ; Luo et al, 2021 ; Rosselot et al, 2021 ; Nevzorova and Cubero, 2023 ; Zacarias-Fluck et al, 2024 ). Several reports from our group and others have highlighted an essential role of the transcription factor c-Myc in endothelial cell function in development ( Baudino et al, 2002 ; He et al, 2008 ; Rodrigues et al, 2008 ; Kokai et al, 2009 ) and disease ( Riu et al, 2002 ; Riu et al, 2003 ; Hurley et al, 2010 ; Florea et al, 2013 ; Rosselot et al, 2019 ; Qi et al, 2022 ).…”

IDENTIFICATION OF IMMUNE RESPONSE AND RNA NETWORK OF RHEUMATOID ARTHRITIS AND MOLECULAR DOCKING OFCELASTRUS PANICULATUSAS POTENTIAL THERAPEUTIC AGENT

“…On the other hand, MYC Proto-Oncogene (MYC) is also one of the top 10 downregulated hub genes. It encodes c-MYC protein which regulates the growth and invasiveness of rheumatoid arthritis synovial fibroblast (RASF) and inhibits apoptosis of RASF leading to promotion of inflammation (Zacarías-Fluck et al, 2024). It also activates immune cells such as T-cells which significantly contribute to the pathogenesis of RA (Zacarías-Fluck et al, 2024).…”

“…It encodes c-MYC protein which regulates the growth and invasiveness of rheumatoid arthritis synovial fibroblast (RASF) and inhibits apoptosis of RASF leading to promotion of inflammation (Zacarías-Fluck et al, 2024). It also activates immune cells such as T-cells which significantly contribute to the pathogenesis of RA (Zacarías-Fluck et al, 2024). Furthermore, Annexin A5 (ANXA5) is one of the hub genes that has been extensively studied for its role in RA (Baek et al, 2017).…”