Axl as a mediator of cellular growth and survival

Abstract

The control of cellular growth and proliferation is key to the maintenance of homeostasis. Survival, proliferation, and arrest are regulated, in part, by Growth Arrest Specific 6 (Gas6) through binding to members of the TAM receptor tyrosine kinase family. Activation of the TAM receptors leads to downstream signaling through common kinases, but the exact mechanism within each cellular context varies and remains to be completely elucidated. Deregulation of the TAM family, due to its central role in mediating cellular proliferation, has been implicated in multiple diseases. Axl was cloned as the first TAM receptor in a search for genes involved in the progression of chronic to acute-phase leukemia, and has since been established as playing a critical role in the progression of cancer. The oncogenic nature of Axl is demonstrated through its activation of signaling pathways involved in proliferation, migration, inhibition of apoptosis, and therapeutic resistance. Despite its recent discovery, significant progress has been made in the development of effective clinical therapeutics targeting Axl. In order to accurately define the role of Axl in normal and diseased processes, it must be analyzed in a cell type-specific context.

Valproic acid (VPA) inhibits the epithelial–mesenchymal transition in prostate carcinoma via the dual suppression of SMAD4

“…These findings support the notion that SMAD4 is absolutely indispensable for the inhibition of EMT by VPA in PCa cells. There may also exist other mechanisms that mediate the EMT-regulating process of VPA, such as PI3K/Akt and ZEB1 (Axelrod and Pienta 2014;Roca et al 2013). And it is reasonable to further compare the different roles of median molecules and draw a panorama of EMT regulation.…”

Gas6 /TAM system: physiological insights and diseases

“…Then a single-pass transmembrane domain (TM) followed by the cytoplasmic tail (intracellular domain) which contains a protein tyrosine kinase (TK) domain at the C-terminal (Figure -1B) [11]. …”

“…The Gas6/TAM system regulates multiple biological processes, including cell survival and proliferation, cell adhesion and migration, thrombus stabilization, and inflammatory cytokine release [19]. Therefore, the role of this system has been found to be important in inflammation, hemostasis, autoimmune disease, nervous, reproductive and vascular systems and cancer [14].…”

“…Role of Gas6/ TAM system in some diseases: has been reported in ischemia/ reperfusion-induced damage, and in the wound healing response to liver injury [11].…”

Inverse regulation of bridging integrator 1 and BCR-ABL1 in chronic myeloid leukemia

“…The biological ligand for AXL receptor is the product of growth arrest-specific gene 6 (Gas6). AXL activation, by Gas6 binding, induces different mechanisms like cell survival, proliferation [19], and migration [20,21]. Recent data reported AXL overexpression in several type of tumors [22][23][24] and its involvement in cancer progression [25] and resistance to therapies [22,26].…”