biostudies-literatureUnknown5(19)Djaafri IKindlin-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 talOncotarget8970-85https://www.ebi.ac.uk/biostudies/studies/S-EPMC4253411biostudies-literatureA novel tumor suppressor function of Kindlin-3 in solid cancer.PMC4253411Daunay ASoulier JSadoux ATeixeira LLebbe CKhayati FFauvel FSetterblad NTost JJanin AMourah SIdbaih APodgorniak MPMenashi SCalvo FDjaafri IfalseA novel tumor suppressor function of Kindlin-3 in solid cancer.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 tal2014-01-01T00:00:00Z2014 Oct2025-04-22T20:38:44.992Z2019-03-27T01:40:47ZS-EPMC42534112534486010.18632/oncotarget.2125