Cytoskeletal dynamics regulates stromal invasion behavior of distinct liver cancer subtypes

Area of Science:

• Oncology
• Cell Biology
• Biophysics

Background:

• Liver cancer drug treatment efficacy is limited by heterogeneous responses across subtypes.
• Functional biophysical phenotypes driving aggressive invasion in liver cancer remain poorly understood.
• Cytoskeletal dynamics are implicated in liver cancer heterogeneity and drug resistance.

Purpose of the Study:

• To investigate how liver cancer subtype heterogeneity influences invasive phenotypes and drug response.
• To link cytoskeletal dynamics to differential invasion profiles and drug resistance.
• To explore the efficacy of targeting biophysical phenotypes in liver cancer.

Main Methods:

• Histological analysis and quantitative 2D invasion metrics.
• Reconstituted 3D hydrogel invasion assays.
• Bioinformatics analysis of cytoskeletal regulation in SNU-475 and HepG2 liver cancer cell lines.

Main Results:

• Cytoskeletal inhibitors differentially affected 2D and 3D migration in SNU-475 (aggressive) and HepG2 cell lines.
• For SNU-475 cells, many cytoskeletal inhibitors reduced 2D migration, but only some affected 3D migration.
• For HepG2 cells, cytoskeletal inhibition impacted proliferation and spheroid growth more than 3D migration.

Conclusions:

• Cytoskeleton-driven phenotypic variations contribute to liver cancer heterogeneity, invasion, and drug resistance.
• Targeting biophysical phenotypes may overcome limitations of traditional drug screens focused solely on tumor growth.
• Understanding cytoskeletal dynamics is crucial for developing effective liver cancer therapies.