Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the importance of mitochondrial fatty acid oxidation (FAO) in cancer metabolism, the biological mechanisms responsible for the FAO in cancer and therapeutic intervention based on catabolic metabolism are not well defined. In this study, we observe that Snail (SNAI1), a key transcriptional repressor of epithelial-mesenchymal transition, enhances catabolic FAO, allowing pro-survival of breast cancer cells in a starved environment. Mechanistically, Snail suppresses mitochondrial ACC2 (ACACB) by binding to a series of E-boxes located in its proximal promoter, resulting in decreased malonyl-CoA level. Malonyl-CoA being a well-known endogenous inhibitor of fatty acid transporter carnitine palmitoyltransferase 1 (CPT1), the suppression of ACC2 by Snail activates CPT1-dependent FAO, generating ATP and decreasing NADPH consumption. Importantly, combinatorial pharmacologic inhibition of pentose phosphate pathway and FAO with clinically available drugs efficiently reverts Snail-mediated metabolic reprogramming and suppresses in vivo metastatic progression of breast cancer cells. Our observations provide not only a mechanistic link between epithelial-mesenchymal transition and catabolic rewiring but also a novel catabolism-based therapeutic approach for inhibition of cancer progression.
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PMID:Snail augments fatty acid oxidation by suppression of mitochondrial ACC2 during cancer progression. 3248 89

Capicua (CIC) is a highly conserved transcriptional repressor that is differentially regulated through mitogen-activated protein kinase (MAPK) signaling or genetic alteration across human cancer. CIC contributes to tumor progression and metastasis through direct transcriptional control of effector target genes. Recent findings indicate that CIC dysregulation is mechanistically linked and restricted to specific cancer subtypes, yet convergence on key downstream transcriptional nodes are critical for CIC-regulated oncogenesis across these cancers. In this review, we focus on how differential regulation of CIC through functional and genetic mechanisms contributes to subtype-specific cancer phenotypes and we propose new therapeutic strategies to effectively target CIC-altered cancers.
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PMID:Capicua in Human Cancer. 3297 89


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