Noted. Inhibiting or downregulating these different active kinases in these cells all showed significant effects on their biology, including proliferation, migration and invasion. Combining inhibitors of these different kinases had a greater effect, in particular a receptor kinase, i.e. EGFR, and a cytoplasmic kinase, i.e. Lyn. SFK signaling networks, in particular Lyn, appeared to be central to the basal cell phenotype, intersecting numerous pathways involving the other activated tyrosine kinases in these cells [41]. Interestingly, Lyn is also present in luminal progenitors, thought to be the cells-of-origin for basal breast cancer, supporting speculation that abnormal Lyn signaling helps drive the basal cancer cell phenotype. Thus several lines of evidence point to a significant involvement of Lyn in solid tumor development, as well as leukaemias. Further, solely deleting or hyper-activating Lyn on its own has little direct influence upon the prevalence of leukaemia or cancer [20,34], but as this enzyme is important for particular neoplasms (reviewed above), it must therefor be concluded that a dysregulation of pathways/substrates/regulators/adaptors, intersected by Lyn, rather than just Lyn itself, is what potentiates these particular cancers and leukaemias.Conclusions Numerous cell lineages of the hematopoietic system (with the notable exception of T-cells), as well as progenitor cells, utilize Lyn in complex signaling pathways,Ingley Cell Communication and Signaling 2012, 10:21 http://www.biosignaling.com/content/10/1/Page 8 ofoften through regulating receptor and/or integrin initiated networks. It’s critical role in B-cell receptor signaling has highlighted its modulating capacity via activating as well as inhibiting down-stream pathways. Phosphorylation and protein-protein interactions regulate Lyn activity, and new data suggests the two isoforms of Lyn, which differ in the presence/absence of a pY motif (pY32), may have different biological functions, potentially explaining its duality in activating and inhibiting signaling. Lyn’s regulation of immune cell function suggests it may be important for immune diseases; indeed dysregulation of Lyn can lead to autoimmune diseases in mice, reminiscent of SLE, asthma and psoriasis. While Lyn rarely appears as an initiator of leukaemogenesis, mounting evidence implicates it in playing a role in maintaining the leukemic phenotype in a variety of liquid cancers, including AML, CML, B-ALL and B-CLL. In addition to being a hematopoietic kinase, Lyn is also expressed in other tissues, and has a recognized oncogenic role in solid cancers of these organs, including prostate, basal breast, and colon cancer, as well as Ewing’s sarcoma and glioblastoma. With several anticancer drugs being potent Lyn inhibitors, it is going to be important to address the role that Lyn and its pathways play in these different neoplasms.Lixisenatide msds Abbreviations SFK: Src Family Kinases; AML: Acute Myeloid Leukaemia; CML: Chronic Myeloid Leukaemia; CLL: Chronic Lymphocytic Leukaemia; B-CLL: B-Cell Chronic Lymphocytic Leukaemia; B-NHL: B-Non Hodgkin’s lymphoma; SH: Src Homology; SLE: Systemic Lupus Erythematosus; BCR: B-Cell Receptor. Competing interests The author declares that PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25768400 he has no competing interests. Authors’ contributions EI organized, wrote and edited the manuscript, as well as designed the figures. Authors’ information EI heads the Cell Signalling Group, WAIMR, Perth, WA 6000, Australia. Additional information on the re.
