Function of Axl receptor tyrosine kinase in non-small cell lung cancer (Review)

Abstract

Axl receptor tyrosine kinase (hereafter Axl) is a member of the tyrosine-protein kinase receptor Tyro3, Axl and proto-oncogene tyrosine-protein kinase Mer family of receptor tyrosine kinases, possessing multiple different functions in normal cells. Axl is overexpressed and activated in numerous different human cancer types, triggering several signaling pathways and enhancing tumor progression. The present review assesses previous studies on the function of Axl in non-small cell lung cancer (NSCLC). Axl is overexpressed in the tumor tissues of a number of patients with NSCLC and is associated with poorer clinical outcomes; it promotes NSCLC tumor growth, invasion/metastasis, drug resistance and the epithelial-mesenchymal transition, thus providing a survival advantage to tumor cells. Therefore, Axl may be a promising target in NSCLC treatment.

Pharmaceutical inhibition of AXL suppresses tumor growth and invasion of esophageal squamous cell carcinoma

“…1B-E ). AKT and ERK signaling are two major branches of AXL signaling ( 4 , 22 , 23 ), thus their responses to R428 were determined; it was identified that R428 treatment suppressed AKT and ERK signaling activation in a dose-dependent manner ( Fig. 1B-E ).…”

“…For example, epidermal growth factor (EGF), which activates the EGF receptor, was discovered to subsequently transactivate AXL (17). In addition, hepatocyte growth factor (HGF) was reported to activate AXL by promoting the formation of HGF receptor MET and AXL complexes (30). However, the pathway involved in the activation of AXL in the two cell lines requires further investigations.…”

Enapotamab vedotin, an AXL-specific antibody-drug conjugate, shows preclinical antitumor activity in non-small cell lung cancer

“…In addition to resistance to EGFRi, AXL overexpression has been associated with resistance to other targeted and chemotherapeutic agents in NSCLC, as recently reviewed (37). The evidence for this association is derived primarily from preclinical studies in vitro, where AXL upregulation was found in cell lines resistant to targeted agents such as PI3K inhibitors (8) or chemotherapeutics like paclitaxel, cisplatin, carboplatin, vincristine, or etoposide (38)(39)(40).…”

The Dual Role of TAM Receptors in Autoimmune Diseases and Cancer: An Overview

“…Among members of TAM receptors, Axl has been extensively studied in several types of cancers [ 113 ]. Reports have demonstrated Axl upregulation in tumors such as prostate [ 114 , 115 , 116 , 117 ], ovarian [ 118 , 119 , 120 , 121 , 122 , 123 ], NSCLC [ 124 , 125 ], OSCC [ 126 , 127 , 128 ], osteosarcoma [ 129 , 130 , 131 ], AML [ 132 ], schwannoma [ 112 ], glioma [ 16 , 133 , 134 , 135 ], and thyroid cancer cell lines [ 106 , 136 ].…”