AXL Tyrosine Kinases: A Growing Isoform Family That Promotes Cancer Pathogenesis

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• AXL receptor tyrosine kinase (RTK) is a key player in various cancers, correlating with poor prognosis and treatment resistance.
• AXL signaling pathways, including PI3K/AKT, MAPK/ERK, JAK/STAT, and NF-κB, drive cancer cell survival, proliferation, migration, and immune evasion.

Purpose of the Study:

• To review the complex signaling mechanisms of AXL receptor tyrosine kinase (RTK).
• To highlight the distinctions between AXL isoforms, particularly the newly identified AXL3.
• To emphasize the importance of understanding AXL isoform functions for developing effective cancer therapies.

Main Methods:

• Literature review of recent studies on AXL receptor tyrosine kinase (RTK) signaling.
• Analysis of AXL isoform structures and their implications for activation and signaling.
• Examination of AXL promoter region for potential transcription factor binding sites.

Main Results:

• A third AXL isoform, AXL3, has been identified, lacking the GAS6 binding domains present in AXL1 and AXL2, suggesting unique activation pathways.
• AXL upregulation in cancer is typically mediated by non-genetic mechanisms, unlike other oncogenic kinases.
• Transcription factors KLF16 and MEIS3 show potential binding to the AXL3 promoter, linking it to oncogenic pathways.

Conclusions:

• Differentiating between AXL isoforms is essential for understanding their roles in cancer.
• Targeted inhibition of AXL shows promise but requires further refinement based on isoform-specific functions.
• Further research into AXL isoform regulation and signaling is critical for advancing targeted cancer therapies.