MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via Regulation of Mitochondrial Oxidative Phosphorylation

MYC (54%) and MCL1 (35%)nHighlight:MYC is a proto-oncogene that encodes a transcription factor associated with cancer cell-cycle progression, proliferation, apoptosis, and biosynthesisnHighlight:Myeloid cell leukemia-1 (MCL1) is an anti-apoptotic Bcl-2 family protein that prevents apoptosisnHighlight:breast CSCs predominantly relied on mitochondrial oxidative phosphorylation (mtOXPHOS)nHighlight:MYC- and MCL1-induced mtOXPHOS led to elevated production of reactive oxygen species (ROS), which in turn induced HIF-1α expressionnHighlight:Dormant pancreatic tumor cells, which exhibit CSC features, rely on mtOXPHOS for survival after oncogene ablationnHighlight:Inhibition of mitochondrial function by metformin eliminates pancreatic CSCsnHighlight:metformin, a mitochondrial complex I inhibitor, reduced mammosphere formation and limited tumor initiationnHighlight:These results suggest that TNBC CSCs exhibit hyperactive mtOXPHOS, which in turn maintains their self-renewal capacity.nHighlight:Hypoxia is a micro-environmental state that activates hypoxia-inducible factor (HIF) signaling, promoting CSCs and tumorigenesisnHighlight:As a byproduct of mtOXPHOS, ROS stabilize HIF proteins, resulting in activation of hypoxia signalingnHighlight:MYC and MCL1 cooperated in the promotion of mtOXPHOS that in turn activated the hypoxia pathway to further potentiate CSC enrichment, revealing novel mechanism(s) by which MYC and MCL1 induce anticancer drug resistancenHighlight:Cancer cells without stem-like features predominantly exhibit an aerobic glycolytic phenotype to produce energy, known as the Warburg effectnHighlight:CSCs display distinct metabolic featuresnHighlight:MYC is also known to participate in mitochondrial metabolic regulation processes, including mitochondrial biogenesis (

  • Li F.
  • Wang Y.
  • Zeller K.I.
  • Potter J.J.
  • Wonsey D.R.
  • O’Donnell K.A.
  • Kim J.W.
  • Yustein J.T.
  • Lee L.A.
  • Dang C.V.
Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis.Mol. Cell. Biol. 2005; 25: 6225-6234
) and glutamine metabolismnHighlight:MCL1 is an anti-apoptotic Bcl-2 family membernHighlight:a cooperative role of MYC and MCL1 on CSC enrichment that, in turn, leads to chemotherapy resistance in MYC– and MCL1-co-amplified TNBC cells and tumorsnHighlight:Genetic and pharmacological inhibition of HIF-1α reduced CSCs and restored chemotherapy actionn]]>

Picture of About Dr. Nathan Goodyear
About Dr. Nathan Goodyear

Dr. Nathan Goodyear, a medical doctor with years of experience in the field of integrative cancer care, has announced the launch of an online training program. This program, available on his new website, will provide individuals with access to video trainings led by Dr. Goodyear himself, covering a range of topics related to integrative cancer care. These trainings will include information on the latest research and techniques in the field, as well as guidance on how to incorporate these approaches into a patient’s overall cancer treatment plan. With this online program, Dr. Goodyear hopes to make his expertise and knowledge more widely accessible, and help more people understand the benefits of integrative cancer care.

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