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PMID:21057534

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Citation

Pittoni, P, Piconese, S, Tripodo, C and Colombo, MP (2011) Tumor-intrinsic and -extrinsic roles of c-Kit: mast cells as the primary off-target of tyrosine kinase inhibitors. Oncogene 30:757-69

Abstract

c-Kit tyrosine kinase receptor and its ligand stem cell factor have multiple functions during development, whereas in adulthood they are mostly needed for stem cell (SC) maintenance and mast cell (MC) biology. c-Kit plays an essential tumor-cell-intrinsic role in many types of cancer, either providing the tumorigenic force when aberrantly activated or conferring stem-like features characterizing the most aggressive variants. A tumor-cell-extrinsic role occurs through c-Kit-dependent accessory cells (such as MCs) that infiltrate tumors and deeply influence their progression. c-Kit-targeted therapy with tyrosine kinase inhibitors (TKIs) may ideally work against both tumor and stromal cells. Here, we summarize the tumor-intrinsic and -extrinsic roles of c-Kit in cancer and discuss TKIs with their on- and off-targets, with a special emphasis on MCs as paradigmatic c-Kit-dependent accomplices for tumor progression.

Links

PubMed Online version:10.1038/onc.2010.494

Keywords

Animals; Antineoplastic Agents/therapeutic use; Humans; Mast Cells/drug effects; Mast Cells/immunology; Mast Cells/metabolism; Mastocytosis/blood supply; Mastocytosis/drug therapy; Mastocytosis/immunology; Mice; Neoplasm Invasiveness; Neoplasms/blood supply; Neoplasms/drug therapy; Neoplasms/enzymology; Neovascularization, Pathologic/drug therapy; Neovascularization, Pathologic/enzymology; Protein Kinase Inhibitors/therapeutic use; Proto-Oncogene Proteins c-kit/antagonists & inhibitors; Proto-Oncogene Proteins c-kit/metabolism; Rats; Stem Cell Factor/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:KIT

involved_in

GO:0042127: regulation of cell population proliferation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:KIT

involved_in

GO:0070662: mast cell proliferation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:KIT

involved_in

GO:0030318: melanocyte differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:KIT

involved_in

GO:0019827: stem cell population maintenance

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete


See also

References

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