期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 178, 期 1, 页码 81-93出版社
WILEY
DOI: 10.1111/bjh.14642
关键词
chronic lymphocytic leukaemia; Cortactin; matrix metalloproteinase-9; B-cell receptor and Ibrutinib
类别
资金
- Ministero dell'Istruzione dell'Universita' e della Ricerca (PRIN)
- Associazione Italiana per la Ricerca sul Cancro AIRC (Milan) (AIRC project) [15397]
- AIRC Regional Project
- CARIVERONA, Regione Veneto on chronic lymphocytic leukaemia
- AIRC (Milan) (AIRC project) [14972]
- Fondazione CARIPARO
Cortactin (CTTN) is a substrate of the Src kinase Lyn that is known to play an actin cytoskeletal regulatory role involved in cell migration and cancer progression following its phosphorylation at Y421. We recently demonstrated that Cortactin is overexpressed in patients with chronic lymphocytic leukaemia (CLL). This work was aimed at defining the functional role of Cortactin in these patients. We found that Cortactin is variably expressed in CLL patients both in the peripheral blood and lymph nodes and that its expression correlates with the release of matrix metalloproteinase 9 (MMP-9) and the motility of neoplastic cells. Cortactin knockdown, by siRNA, induced a reduction in MMP-9 release as well as a decrease of migration capability of leukaemic B cells in vitro, also after chemotactic stimulus. Furthermore, Cortactin phosphorylation was lowered by the Src kinase-inhibitor PP2 with a consequent decrease of MMP-9 release in culture medium. An impaired migration, as compared to control experiments without Cortactin knockdown, was observed following CXCL12 triggering. Reduced Cortactin expression and phosphorylation were also detected both in vivo and in vitro after treatment with Ibrutinib, a Btk inhibitor. Our results highlight the role of Cortactin in CLL as a check-point molecule between the BCR and CXCR4 signalling pathways.
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