====== Tumorigenesis ======
[[Carcinogenesis]] or oncogenesis or tumorigenesis is literally the 'creation' of [[cancer]]. It is a process by which normal cells are transformed into cancer cells. It is characterized by a progression of changes at the cellular, genetic and epigenetic level that ultimately reprogram a cell to undergo uncontrolled cell division, thus forming a malignant mass.
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Tumorigenesis is associated with elevated [[glucose]] and [[glutamine]] consumption, but how [[cancer]] [[cell]]s can sense their levels to activate [[lipid]] synthesis is unknown.
Cheng et al. revealed that [[ammonia]], released from [[glutamine]], promotes [[lipogenesis]] via activation of [[Sterol regulatory element-binding protein]]s ([[SREBP]]s), [[Endoplasmic Reticulum-Bound Transcription Factor]]s that play a central role in [[lipid]] metabolism. Ammonia activates the dissociation of [[glucose]]-regulated, N-glycosylated SREBP-cleavage-activating protein ([[SCAP]]) from insulin-inducible gene protein (Insig), an endoplasmic reticulum-retention protein, leading to SREBP translocation and lipogenic gene expression. Notably, 25-hydroxycholesterol blocks ammonia to access its binding site on SCAP. Mutating aspartate D428 to alanine prevents ammonia binding to SCAP, abolishes SREBP-1 activation, and suppresses tumor growth. The study characterizes the unknown role, opposite to [[sterol]]s, of [[ammonia]] as a key activator that stimulates [[SCAP]]-Insig dissociation and [[SREBP]]-1 activation to promote [[tumor growth]] and demonstrates that [[SCAP]] is a critical sensor of [[glutamine]], [[glucose]], and [[sterol]] levels to precisely control lipid synthesis
((Cheng C, Geng F, Li Z, Zhong Y, Wang H, Cheng X, Zhao Y, Mo X, Horbinski C, Duan W, Chakravarti A, Cheng X, Guo D. Ammonia stimulates SCAP/Insig dissociation and SREBP-1 activation to promote lipogenesis and tumour growth. Nat Metab. 2022 May 9. doi: 10.1038/s42255-022-00568-y. Epub ahead of print. PMID: 35534729.)).

===== Glioma Tumorigenesis =====

[[Gliomagenesis]]