Related Experiment Video

Updated: Oct 25, 2025

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
07:26

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

Published on: January 31, 2025

745

Hedgehog/GLI1 Transcriptionally Regulates FANCD2 in Ovarian Tumor Cells: Its Inhibition Induces HR-Deficiency and

Chinnadurai Mani1, Kaushlendra Tripathi2, Sandeep Chaudhary3

  • 1Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

Neoplasia (New York, N.Y.)
|August 11, 2021
PubMed

Insights

This study reveals a new role for GLI1 in ovarian cancer, showing that inhibiting it can make cancer cells more sensitive to PARP inhibitors by increasing DNA damage and improving treatment response.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Ovarian cancer (OC) is a lethal malignancy with limited targeted therapies and frequent recurrence.
  • Poly (ADP-ribose) polymerase inhibitors (PARPi) show efficacy but are limited to patients with BRCA mutations.

Purpose of the Study:

  • To investigate the role of Hedgehog (Hh) transcription factor Glioma associated protein 1 (GLI1) in ovarian cancer.
  • To explore the potential of GLI1 inhibition in combination with PARP inhibitors for OC treatment.

Main Methods:

  • Investigated GLI1 regulation of the FANCD2 gene in OC cells.
  • Assessed the effects of GLI1 inhibition on homologous recombination (HR) proficiency, replication stress, and cell viability.
  • Evaluated the synergistic effects of combined GLI1 and PARP inhibition on DNA damage, cytotoxicity, and in vivo anticancer responses.

Main Results:

  • GLI1 inhibition in HR-proficient OC cells induced HR deficiency (BRCAness) and replication stress.
  • Combination therapy of GLI1 and PARP inhibitors demonstrated synergistic lethality in OC cells.
  • Combined treatment enhanced DNA damage, cytotoxicity, and showed significant in vivo anticancer activity.

Conclusions:

  • GLI1 plays a novel regulatory role in DNA repair pathways in ovarian cancer.
  • Targeting GLI1 in combination with PARP inhibitors offers a promising therapeutic strategy for ovarian cancer, potentially expanding treatment options beyond BRCA-mutated cases.
Keywords:
FANCD2GANT61GLI1OlaparibOvarian Cancerand Homologous recombination deficiency

More Related Videos

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

6.9K
Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays04:07

Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays

Published on: February 24, 2023

1.9K

Related Concept Videos

Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.8K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.4K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

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.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.3K
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...
4.7K