New insights into the pathophysiology of the tuberous sclerosis complex: Crosstalk of mTOR- and hippo-YAP pathways in cell growth
نویسندگان
چکیده
Tuberous Sclerosis Complex (TSC) is a genetic disease causing uncontrolled growth of hamartomas involving different organ systems. In the last decade, dysregulation of the mTORC1 pathway was shown to be a main driver of tumor growth in TSC. Recently, a new crosstalk was detected between the mTORC1 and the Hippo-YAP pathway, another major cell signaling cascade controlling cell growth and organ size. Elucidating this connection is an important step in understanding the complexity of TSC, enabling new pharmacological targets and therapeutical options.
منابع مشابه
Regulation of YAP by mTOR and autophagy reveals a therapeutic target of tuberous sclerosis complex
Genetic studies have shown that the tuberous sclerosis complex (TSC) 1-TSC2-mammalian target of Rapamycin (mTOR) and the Hippo-Yes-associated protein 1 (YAP) pathways are master regulators of organ size, which are often involved in tumorigenesis. The crosstalk between these signal transduction pathways in coordinating environmental cues, such as nutritional status and mechanical constraints, is...
متن کاملYAP enters the mTOR pathway to promote tuberous sclerosis complex
Mutations in tuberous sclerosis complex 1 (TSC1) or TSC2 predispose to angiomyolipomas and lymphangioleiomyomatosis in a mTOR-dependent manner. In these mesenchymal lesions, mTOR suppresses macroautophagy-mediated lysosomal degradation of YAP, which is a transcriptional coactivator of Hippo pathway and is required for the tumorigenesis of TSC. Therapeutic applications for TSC and other diseases...
متن کاملThe Role of Mammalian Target of Rapamycine Signaling Pathway in Central Nervous System Cancers: A Review
Mammalian mechanistic target of rapamycine (mTOR) is a conserved serine/threonine kinase in the cellular PI3K/Akt/mTOR signaling pathway. This pathway is modified by cellular alterations such as level of energy, growth factors, stresses, as well as the increased environmental level of cancerous cytokines. In general, increase of this kinase protein function is seen in various types of cancers, ...
متن کاملIdentifying significant crosstalk of pathways in tuberous sclerosis complex.
OBJECTIVE Tuberous sclerosis complex (TSC) is the second most common phakomatosis and is characterized by the formation of benign hamartomas and low-grade neoplasms in multiple organ systems. In this study, our objective here was to explore the interaction and crosstalk between pathways in response to tuberous sclerosis complex. MATERIALS AND METHODS We enriched the significant pathways and m...
متن کاملUnited at last: the tuberous sclerosis complex gene products connect the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) signalling.
The molecular interplay between the phosphoinositide 3-kinase (PI3K) pathway and mammalian target of rapamycin (mTOR) signalling in the control of cell growth and proliferation has been the subject of much interest and debate amongst cell biologists. A recent escalation of research in this area has come from the discovery of the tuberous sclerosis complex gene products, tuberin and hamartin, as...
متن کامل