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Article Dans Une Revue Oncotarget Année : 2014

A novel tumor suppressor function of Kindlin-3 in solid cancer

Résumé

Kindlin-3 (FERMT-3) is known to be central in hemostasis and thrombosis control and its deficiency disrupts platelet aggregation and causes Leukocyte Adhesion Deficiency disease. Here we report that Kindlin-3 has a tumor suppressive role in solid cancer. Our present genetic and functional data show that Kindlin-3 is downregulated in several solid tumors by a mechanism involving gene hypermethylation and deletions. In vivo experiments demonstrated that Kindlin-3 knockdown in 2 tumor cell models (breast cancer and melanoma) markedly increases metastasis formation, in accord with the in vitro increase of tumor cell malignant properties. The metastatic phenotype was supported by a mechanism involving alteration in β3-integrin activation including decreased phosphorylation, interaction with talin and the internalization of its active form leading to less cell attachment and more migration/invasion. These data uncover a novel and unexpected tumor suppressor role of Kindin-3 which can influence integrins targeted therapies development
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cea-04651814 , version 1 (17-07-2024)

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Ibtissem Djaafri, Farah Khayati, Suzanne Menashi, Jorg Tost, Marie-Pierre Podgorniak, et al.. A novel tumor suppressor function of Kindlin-3 in solid cancer. Oncotarget, 2014, 5 (19), pp.8970-8985. ⟨10.18632/oncotarget.2125⟩. ⟨cea-04651814⟩
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