Receptor Tyrosine Kinase Signaling in Cancer Biology

Receptor tyrosine kinases (RTKs) form a large family of cell-surface enzymes that regulate fundamental processes such as proliferation, survival, migration and differentiation. Ligand binding induces dimerisation and autophosphorylation of RTKs, creating docking sites for intracellular effectors that activate pathways including RAS–MAPK, PI3K–AKT and STAT. Dysregulation of RTK signalling through gene amplification, activating mutation, chromosomal translocation or aberrant ligand expression underpins the pathogenesis of many cancers. Atypical RTKs of the ROR family (ROR1, ROR2) engage non-canonical Wnt ligands to govern cytoskeletal dynamics, cell polarity and resistance to therapy. Aberrant ROR expression contributes to intra-tumour heterogeneity, invasion and metastasis by co-opting mechanisms such as Golgi-mediated secretory polarisation and invadopodia formation. Recent advances have dissected these molecular circuits and translated them into novel biomarkers and targeted agents, highlighting RTK signalling as a linchpin of precision oncology.

Research from Nature Portfolio

Recent studies have demonstrated that Ror2 signalling recruits the intraflagellar transport component IFT20 to regulate Golgi microtubule nucleation and ribbon assembly in tumour cells lacking primary cilia. By orchestrating Golgi-derived secretion and polarised membrane remodelling, this pathway promotes invadopodia formation and enhances invasive capacity. These findings pinpoint Golgi structure and trafficking as critical downstream effectors of atypical RTK activity and suggest new intervention points to curb metastasis.

Receptor Tyrosine Kinase Signaling in Cancer Biology publication trend

The graph below shows the total number of articles in receptor tyrosine kinase signaling in cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

Receptor tyrosine kinase (RTK): A cell-surface enzyme receptor that dimerises upon ligand binding and phosphorylates tyrosine residues to initiate intracellular signalling cascades.

ROR1 and ROR2: Atypical RTKs belonging to the ROR family that bind non-canonical Wnt ligands (e.g. Wnt5a) to regulate migration, survival and invasive behaviour in cancers.

Invadopodia: Actin-rich, membrane-bound protrusions formed by cancer cells to degrade extracellular matrix and facilitate local invasion.

Exosome: Small extracellular vesicles of endosomal origin released by cells that carry proteins, lipids and nucleic acids for intercellular communication and biomarker discovery.

Autophosphorylation: The process by which a kinase enzyme phosphorylates its own tyrosine residues, typically following receptor dimerisation, to create docking sites for downstream signalling proteins.

References

1. Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness. Scientific Reports (2017).
2. ROR1-STAT3 signaling contributes to ovarian cancer intra-tumor heterogeneity. Cell Death Discovery (2023).
3. Exosomal ROR1 in peritoneal fluid identifies peritoneal disseminated PDAC and is associated with poor survival. Frontiers in Immunology (2024).
4. A Small Molecule Targeting the Intracellular Tyrosine Kinase Domain of ROR1 (KAN0441571C) Induced Significant Apoptosis of Non-Small Cell Lung Cancer (NSCLC) Cells. Pharmaceutics (2023).