Tag Archives: ferroptosis

Do we finally know what MYC is doing in cancer?

Tens of thousands of papers have been written on what MYC might be doing in cancer.  I’ve been reading about Myc for years, and my notes on Myc  contain 60,000+ characters. Cancer cells must love MYC as around 70% of human cancers overexpress the MYC protein, which is a transcription factor turning on the expression of at least 1,500 genes.  Others say 2,000 ( 10% of all protein coding genes).  “Whatever the latest trend in cancer biology — cell cycle, cell growth, apoptosis, metabolism, cancer stem cells, microRNAs, angiogenesis, inflammation — Myc is there regulating most of the key genes”  [ Cell vol. 151 pp. 11 – 13 ’12 ].   An intriguing theory is that Myc is part of the Matthew syndrome — Matthew 25:29
“For everyone who has will be given more, and he will have an abundance.”  Translating this into molecular biological terms, Myc acts to amplify the transcriptional state of any gene which is actively being transcribed.

The old idea that cells just up and died when they got sick, is pretty much gone.  There are various types of cell death, each of which has an intricately programmed mechanism — apoptosis, ferroptosis, pyroptosis, and necroptosis.  The latter is common on cancer, particularly when attacked by the immune system. [ Proc. Natl. Acad. Sci. vol. 117 pp. 19982 – 19993 20 ] says that MYC acts as an antinecroptosis factor by inhibiting the interaction of RIPK1 and RIPK3 which goes on to trigger necroptosis. This may be why cancer cells so love MYC.  What is particularly fascinating (to neurologists at least) is that further along the path to necroptosis another protein (MLKL) forms cytoplasmic amyloid fibers as part of the process.  So here is a physiological use for amyloid (even though the net result is death).