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

作者:Djaafri Ibtissem; Khayati Farah; Menashi Suzanne; Tost Jorg; Podgorniak Marie Pierre; Sadoux Aurelie; Daunay Antoine; Teixeira Luis; Soulier Jean; Idbaih Ahmed; Setterblad Niclas; Fauvel Francoise; Calvo Fabien; Janin Anne; Lebbe Celeste; Mourah Samia*
来源:Oncotarget, 2014, 5(19): 8970-8985.
DOI:10.18632/oncotarget.2125

摘要

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 beta 3-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.

  • 出版日期2014-10-15
  • 单位中国地震局