AXL is a receptor tyrosine kinase commonly associated with a variety of human cancers. Along with its ligand Gas6 (growth arrest-specific protein 6), AXL is emerging as an important regulator of neuroendocrine development and function. AXL signaling in response to Gas6 binding impacts neuroendocrine structure and function at the level of the brain, pituitary, and gonads. During development, AXL has been identified as an upstream inhibitor of gonadotropin receptor hormone (GnRH) production and also plays a key role in the migration of GnRH neurons from the olfactory placode to the forebrain. AXL is implicated in reproductive diseases including some forms of idiopathic hypogonadotropic hypogonadism and evidence suggests that AXL is required for normal spermatogenesis. Here, we highlight research describing AXL/Gas6 signaling mechanisms with a focus on the molecular pathways related to neuroendocrine function in health and disease. In doing so, we aim to present a concise account of known AXL/Gas6 signaling mechanisms to identify current knowledge gaps and inspire future research.
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| http://dx.doi.org/10.3389/fendo.2023.1212104 | DOI Listing |
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Immunology Laboratory, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, 700019, West Bengal, India. Electronic address:
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Cell Commun Signal
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Department of Biomedical Sciences, Colorado State University, 1617 Campus Delivery, Fort Collins, CO, 80523, USA.
Background: Gonadotropin-releasing hormone (GnRH) receptors are essential for reproduction and are expressed in numerous urogenital, reproductive, and non-reproductive cancers. In addition to canonical G protein-coupled receptor signaling, GnRH receptors functionally interact with several receptor tyrosine kinases. AXL is a receptor tyrosine kinase expressed in numerous tissues as well as multiple tumors.
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Front Endocrinol (Lausanne)
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Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
AXL is a receptor tyrosine kinase commonly associated with a variety of human cancers. Along with its ligand Gas6 (growth arrest-specific protein 6), AXL is emerging as an important regulator of neuroendocrine development and function. AXL signaling in response to Gas6 binding impacts neuroendocrine structure and function at the level of the brain, pituitary, and gonads.
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Department of Urology, Keio University School of Medicine, 160-8582, Tokyo, Japan.
Background: Cabozantinib is an oral tyrosine kinase inhibitor in renal cell carcinoma (RCC), whose targets include oncogenic AXL and unique ligand GAS6. Critical gaps in basic knowledge need to be addressed to devise an exclusive biomarker and candidate when targeting the AXL/GAS6 axis.
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