Related Experiment Video

Updated: Oct 13, 2025

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
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Intrinsic and Extrinsic Control of Hepatocellular Carcinoma by TAM Receptors

Viola Hedrich1, Kristina Breitenecker1, Leila Djerlek1

  • 1Comprehensive Cancer Center, Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, 1090 Vienna, Austria.

Cancers
|November 13, 2021
PubMed

Insights

TAM receptors (Tyro3, Axl, MerTK) are key drivers in hepatocellular carcinoma (HCC) progression and chemoresistance. Targeting these receptors may offer novel therapeutic strategies for liver cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Hepatocellular carcinoma (HCC) presents a significant global health challenge with high mortality due to limited advanced-stage treatment options.
  • The TAM receptor tyrosine kinases (Tyro3, Axl, MerTK) play crucial roles in cancer biology, regulating inflammation, vascular integrity, and chemotherapy resistance.

Purpose of the Study:

  • To review the multifaceted roles of TAM receptors in hepatocellular carcinoma (HCC) progression.
  • To explore the intrinsic and extrinsic mechanisms by which TAM receptors influence HCC.
  • To assess the potential of TAM receptor inhibition as a therapeutic strategy for HCC.

Main Methods:

  • Literature review focusing on the function of TAM receptors (Tyro3, Axl, MerTK) in HCC.
  • Analysis of TAM receptor signaling pathways, including ligand binding (Gas6, Protein S) and downstream effects.
  • Evaluation of TAM receptor involvement in HCC cell plasticity, metastasis, immune evasion, fibrogenesis, and chemoresistance.

Main Results:

  • TAM receptors intrinsically control HCC by modulating epithelial cell plasticity and promoting metastatic traits.
  • Extrinsically, TAM receptors influence HCC progression through immune cell infiltration and fibrogenesis, varying with HCC etiology.
  • TAM receptors contribute to chemoresistance against tyrosine kinase inhibitors and immune checkpoint blockade in HCC.

Conclusions:

  • TAM receptors are critical regulators of both intrinsic and extrinsic HCC progression.
  • Understanding TAM receptor functions is essential for developing effective therapeutic strategies against liver cancer.
  • Inhibition of TAM receptors represents a promising avenue for novel HCC treatments.
Keywords:
AxlMerTKTAMTyro3chemoresistancehepatocellular carcinomareceptor tyrosine kinasetherapytumor microenvironment

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