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m-TOR

Regulates translational control of different mRNAs and proteins.

mTOR refers to the mammalian target of rapamycin, and is a kinase enzyme inside the cell that collects and interprets growth and survival signals received by tumor cells.

A kinase that integrates a variety of signaling pathways regulating cellular growth, cellular proliferation, and survival.

mTOR enzyme is a component of two distinct complexes, mTOR complex 1 and mTOR complex 2.

These complexes activate pathways that exhibit crosstalk.

When the kinase activity of mTOR is activated, its downstream effectors, the synthesis of cell cycle proteins such as cyclin D and hypoxia-inducible factor-1a (HIF-1a) are increased. HIF-1a then stimulates VEGF.

mTOR kinase, when activated, suppresses autophagy and when not activated promotes it.

If mTOR kinase is activated, determines whether the tumor cell produces key proteins needed for proliferation, growth, survival, and angiogenesis.

mTOR is activated in tumor cells by various mechanisms including growth factor surface receptor tyrosine kinases, oncogenes, and loss of tumor suppressor genes.

Activating factors are important for malignant transformation and progression.

Important in the biology of renal cancer because of its function in regulating HIF-1a levels.

Mutation or loss of the von Hippel Lindau tumor-suppressor gene is common in RCC and is manifested by reduced degradation of HIF-1a. In RCC tumors, activated mTOR further exacerbates accumulation of HIF-1a by increasing synthesis of this transcription factor and its angiogenic target gene products.

mTOR signaling is hyperactive in sporadic sacral chordomas.

Key role in cell growth, protein translation, autophagy and metabolism.

Activation contributes to many tumor types.

Regulates cell growth, and acts as intermediary in a variety of cell signaling events that control cell proliferation, angiogenesis and survival.

mTOR pathway there is a central role in the regulation of cell growth, and is dysregulated in multiple cancers.

This pathway stimulates protein synthesis following input from growth factors, hormones, nutrients and other stimulants.

mTORC (mTOR Complex) plays a crucial and vascular stenosis that results from mechanical endothelial injury.

mTORC pathway is involved in the vascular lesions associated with antiphospholipid syndrome.

Pathway is involved in critical cellular functions such as protein degradation, angiogenesis, and his most is regulated in patients with poor prognostic factors such as high nuclear grades.

Mutations in the p110alpha subunit of PI3K, called PIK3CA, are often responsible for activation of the phosphtidylinositol 3 kinase (PI3K)/AKY/mammalian target of rapamycin (MTOR) pathway, reported in various cancers.

PIK3CA mutations can cause neoplastic transformation, probable cancer progression and with mTOR pathway are often DYSREGULATED in breast and gynecological cancers.

PIk3CA mutations have been reported an approximately 18% of breast, 17-33% of cervical, 39% of endometrial, and 12% of ovarian cancers (Engleman JA).

m-TOR pathway upregulated in many human cancers and involves downstream signaling fromP13L/Akt that leads to phosphorylationm-TOR and to activation of substrate p70S6K, which in turn promotes mRNA translation, cell cycle progression an angiogenesis.

Regulates two downstream proteins P70 S6 kinase and 4EBP-1, which are important in helping cells to produce more protein.

A serine/threonine kinase regulates cell growth and proliferation.

Hypoxia inducible factor and hypoxia inducible factor target genes are upregulated by mTOR, and this pathway is important in the pathophysiology of renal cancer.

Temsirolimus and everolimus are mTOR inhibitors.

The mammalian target of rapamycin (m-TOR) inhibitors can produce hyperlipidemia and hyperglycemia.

mTOR inhibitors can shrink or stabilize renal angiomyolipomas, facial angiofibromas, lymphangiomyomatosis and subependymal giant cell astrocytomas.

In renal cell carcinoma MTOR pathway activation correlates with survival and poor pathologic prognostic features.

 

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