Browsing by Subject "Focal adhesion kinase"

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    Focal adhesion kinase and cancer
    (Murcia : F. Hernández, 2009) Golubovskaya1, Vita M.; Kweh, Frederick A.; Cance, William G.
    Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that resides at the sites of integrin clustering, known as focal adhesions. The FAK protein has a molecular mass of 125kDa and is encoded by the FAK gene located on human chromosome 8q24. Structurally, FAK consists of an amino-terminal regulatory FERM domain, a central catalytic kinase domain, two proline-rich motifs, and a carboxy-terminal focal adhesion targeting domain. FAK has been shown to be an important mediator of cell growth, cell proliferation, cell survival and cell migration, all of which are often dysfunctional in cancer cells. Our lab was the first to isolate FAK from primary human tissue and link it to the process of tumorigenesis. We analyzed FAK mRNA expression in normal, invasive and metastatic human tissues and demonstrated through Northern blot analysis that normal tissues had very low levels of FAK mRNA while primary and metastatic tumors significantly overexpressed FAK. We also demonstrated and confirmed FAK overexpression in colorectal carcinoma and liver metastases with real-time PCR. In this review we summarized immunohistochemical data of FAK expression and role in different cancer types tumors and discussed FAK inhibition therapy approaches.
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    New insights into FAK function and regulation during spermatogenesis
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Gungor-Orduer, N. Ece; Mruk, Dolores D.; Wan, Hin-ting; Wong, Elissa W.P.; Celik-Ozenci, Ciler; Lie, Pearl P.Y.; Cheng, C. Yan
    Germ cell transport across the seminiferous epithelium during the epithelial cycle is crucial to spermatogenesis, although molecular mechanism(s) that regulate these events remain unknown. Studies have shown that spatiotemporal expression of crucial regulatory proteins during the epithelial cycle represents an efficient and physiologically important mechanism to regulate spermatogenesis without involving de novo synthesis of proteins and/or expression of genes. Herein, we critically review the role of focal adhesion kinase (FAK) in coordinating the transport of spermatids and preleptotene spermatocytes across the epithelium and the blood-testis barrier (BTB), respectively, along the apical ectoplasmic specialization (ES) – blood-testis barrier – basement membrane (BM) functional axis during spermatogenesis. In the testis, p-FAK-Tyr397 and p-FAKTyr407 are spatiotemporally expressed during the epithelial cycle at the actin-rich anchoring junction known as ES, regulating cell adhesion at the Sertolispermatid (apical ES) and Sertoli cell-cell (basal ES) interface. Phosphorylated forms of FAK exert their effects by regulating the homeostasis of F-actin at the ES, mediated via their effects on actin polymerization so that microfilaments are efficiently re-organized, such as from their “bundled” to “de-bundled/branched” configuration and vice versa during the epithelial cycle to facilitate the transport of: (i) spermatids across the epithelium, and (ii) preleptotene spermatocytes across the BTB. In summary, p-FAK-Tyr407 and p-FAK-Tyr397 are important regulators of spermatogenesis which serve as molecular switches that turn “on” and “off” adhesion function at the apical ES and the basal ES/BTB, mediated via their spatiotemporal expression during the epithelial cycle. A hypothetical model depicting the role of these two molecular switches is also proposed.