JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

CAPG Regulates Doxorubicin Resistance in Hepatocellular Carcinoma Cells via TGFB1/Smad/Nrf2 Signalling Pathway

  • 0Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
Journal of Cellular and Molecular Medicine +

|

September 22, 2025

|

September 22, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Cytoskeleton-associated protein G (CAPG) is upregulated in liver cancer, driving progression and doxorubicin resistance. Targeting CAPG offers a new strategy to improve treatment outcomes for hepatocellular carcinoma patients.

Area Of Science

  • Oncology
  • Molecular Biology
  • Biochemistry

Background

  • Hepatocellular carcinoma (HCC) presents significant challenges due to limited treatment options and chemoresistance.
  • Cytoskeleton-associated protein G (CAPG) has emerged as a potential factor in cancer development.

Purpose Of The Study

  • To investigate the role of CAPG in HCC progression and its association with doxorubicin (Dox) resistance.
  • To elucidate the molecular mechanisms underlying CAPG's function in HCC and chemoresistance.

Main Methods

  • Bioinformatics analysis
  • Immunohistochemistry
  • Cell-based assays
  • Animal models
  • Gene Set Enrichment Analysis (GSEA)

Main Results

  • CAPG was significantly upregulated in HCC tissues and cell lines.
  • High CAPG expression correlated with poor survival and adverse clinicopathological features.
  • CAPG knockdown reduced viability and proliferation in Dox-resistant HCC cells, while overexpression increased resistance.
  • CAPG modulates ferroptosis via the TGFB1/Smad2/NRF2 pathway.
  • CAPG knockdown combined with Dox inhibited tumor growth in vivo.

Conclusions

  • CAPG is a key regulator of HCC progression and chemoresistance.
  • CAPG serves as a potential prognostic biomarker for HCC.
  • Targeting CAPG presents a promising therapeutic strategy to overcome doxorubicin resistance in HCC.

Keywords:

Related Concept Videos

TGF - β Signaling Pathway 01:16

10.5K

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...

Abnormal Proliferation 02:23

5.1K

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...

mTOR Signaling and Cancer Progression 03:03

4.6K

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...

Interactions Between Signaling Pathways 01:19

7.2K

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...

GPCRs Regulate Adenylyl Cylase Activity 01:09

7.3K

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...