Specifically, TGF-β1 promotes tumor progression by inducing a switch from an epithelial to a mesenchymal/migratory phenotype in HCC cells, reducing mitochondrial respiration and enhancing glutamine transporter SLC7A5b (Solute Carrier Family 7 Member 5), glutaminase 1, and pentose phosphate cycle [74]. The latter provides precursors for nucleotide synthesis and prevents oxidative stress and redox homeostasis. https://www.mdpi.com/2072-6694/12/10/2819
Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849637/
However, after careful inspection, it becomes apparent that its benefits for cell growth and survival are not yet resolved.
The Warburg Effect has been proposed to be an adaptation mechanism to support the biosynthetic requirements of uncontrolled proliferation (Figure 2, Key Figure). In this scenario, the increased glucose consumption is used as a carbon source for anabolic processes needed to support cell proliferation [17, 26–32]. This excess carbon is used for the de novo generation of nucleotides, lipids, and proteins and can be diverted into multiple branching pathways that emanate from glycolysis.
Acta Pharmaceutica Sinica B Volume 14, Issue 3, March 2024, Pages 953-1008 Acta Pharmaceutica Sinica B REVIEW Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer Author links open overlay panelMinru Liao a †, Dahong Yao b †, Lifeng Wu a †, Chaodan Luo d, Zhiwen Wang a b c, Jin Zhang c, Bo Liu a https://www.sciencedirect.com/science/article/pii/S2211383523004719
New Clarity on the Warburg Effect SubscribeExit Disclaimer January 13, 2021, by Alba Luengo, Zhaoqi Li, and Matthew Vander Heiden https://www.cancer.gov/research/key-initiatives/ras/news-events/dialogue-blog/2021/vander-heiden-warburg-effect