Related Experiment Videos

Effect of ARHGAP9 on Chemoresistance in High-Risk Advanced Retinoblastoma via the Rac1/β-Catenin/LEF1 Signaling Axis

Wenping Song1,2, Ruijie Li3, Xuan Wu3

  • 1Department of Pharmacy, HNHC Key Laboratory of Anti-tumor Drug Research (Henan Cancer Hospital), Henan Engineering Research Center for Tumor Precision Medicine and Comprehensive Evaluation, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.

Investigative Ophthalmology & Visual Science
|August 19, 2026
PubMed
Abstract

Insights

Rho GTPase-activating protein 9 (ARHGAP9) impacts chemotherapy resistance in retinoblastoma (RB). Restoring ARHGAP9 expression can improve drug response, suggesting its potential as a therapeutic target for high-risk RB.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • High-risk advanced retinoblastoma (RB) exhibits resistance to adjuvant chemotherapy, leading to recurrence and metastasis.
  • Reduced expression of Rho GTPase-activating protein 9 (ARHGAP9) was previously observed in etoposide-resistant RB cells.

Purpose of the Study:

  • To investigate the role of ARHGAP9 in chemoresistance in high-risk advanced RB.
  • To explore ARHGAP9 as a potential prognostic indicator or therapeutic target.

Main Methods:

  • Genomic and epigenomic analyses of peripheral blood from RB patients.
  • In vitro and in vivo studies using ARHGAP9-silenced and ARHGAP9-overexpressing RB cell lines.
  • Functional assays to elucidate the molecular mechanisms of ARHGAP9 in drug response.

Main Results:

  • ARHGAP9 knockdown decreased sensitivity to carboplatin and etoposide; ARHGAP9 overexpression restored drug sensitivity.
  • ARHGAP9 downregulation enhanced Rac1 activity, promoting Rac1-β-catenin interaction and nuclear accumulation.
  • This pathway led to increased LEF1-β-catenin complex formation and upregulation of c-Myc, cyclin D1, and Bcl-2, contributing to chemoresistance.

Conclusions:

  • ARHGAP9 modulates drug responses in RB through the Rac1/β-catenin/LEF1 signaling axis.
  • ARHGAP9 plays a significant role in chemotherapy resistance in high-risk advanced RB.
  • ARHGAP9 is a potential prognostic marker and therapeutic target for advanced high-risk RB.

Related Concept Videos

The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Abnormal Proliferation02:23

Abnormal Proliferation

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 daughter...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...