Nat Rev Cancer. 2014 Dec;14(12):769-85. doi: 10.1038/nrc3847.
The TYRO3, AXL (also known as UFO) and MERTK (TAM) family of receptor tyrosine kinases (RTKs) are aberrantly expressed in multiple haematological and epithelial malignancies. Rather than functioning as oncogenic drivers, their induction in tumour cells predominately promotes survival, chemoresistance and motility. The unique mode of maximal activation of this RTK family requires an extracellular lipid–protein complex. For example, the protein ligand, growth arrest-specific protein 6 (GAS6), binds to phosphatidylserine (PtdSer) that is externalized on apoptotic cell membranes, which activates MERTK on macrophages. This triggers engulfment of apoptotic material and subsequent anti-inflammatory macrophage polarization. In tumours, autocrine and paracrine ligands and apoptotic cells are abundant, which provide a survival signal to the tumour cell and favour an anti-inflammatory, immunosuppressive microenvironment. Thus, TAM kinase inhibition could stimulate antitumour immunity, reduce tumour cell survival, enhance chemosensitivity and diminish metastatic potential.
TYRO3、AXL（也称为 UFO）和 MERTK（TAM）受体酪氨酸激酶家族在多种血液系统和上皮恶性肿瘤中异常表达。它们的诱导在肿瘤细胞中主要促进存活、化学抗性和运动性，而不是作为致癌驱动因素。这种 RTK 家族的独特最大激活方式需要一个细胞外脂质-蛋白复合物。例如，蛋白配体生长停滞特异性蛋白 6（GAS6）与细胞外的磷脂酰丝氨酸（PtdSer）结合，PtdSer 在外源化的凋亡细胞膜上，这激活了巨噬细胞上的 MERTK。这触发了对凋亡物质的吞噬作用，并随后导致抗炎性巨噬细胞极化。在肿瘤中，自分泌和旁分泌配体和凋亡细胞很丰富，这为肿瘤细胞提供了生存信号，并有利于抗炎性、免疫抑制性的微环境。因此，TAM 激酶抑制可能会刺激抗肿瘤免疫、降低肿瘤细胞的存活率、增强化学敏感性和降低转移潜力。
