ArticleMolecular pharmaceutics2012
The transcription factor GCF2 is an upstream repressor of the small GTPAse RhoA, regulating membrane protein trafficking, sensitivity to doxorubicin, and resistance to cisplatin.
Article in Molecular pharmaceutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
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- RhoA-ROCK2 signaling possesses complex pathophysiological functions in cancer progression and shows promising therapeutic potential.Cancer cell international · 2024Review
- The clinical significance and oncogenic function of LRRFIP1 in pancreatic cancer.Discover oncology · 2024Article
- Genomic Landscape and Potential Regulation of RNA Editing in Drug Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry.Prostate cancer and prostatic diseases · 2022Article
- The EphA4 Signaling is Anti-catabolic in Synoviocytes but Pro-anabolic in Articular Chondrocytes.Calcified tissue international · 2020Article
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- RhoA/ROCK pathway: implication in osteoarthritis and therapeutic targets.American journal of translational research · 2019Review
- Transcriptional and post-transcriptional regulation of the genes encoding the small GTPases RhoA, RhoB, and RhoC: implications for the pathogenesis of human diseases.Cellular and molecular life sciences : CMLS · 2018Review
- Genome-wide analysis of alternative transcripts in human breast cancer.Breast cancer research and treatment · 2015Article
- Autophagy negatively regulates early axon growth in cortical neurons.Molecular and cellular biology · 2013Article
- Roles of rho GTPases in intracellular transport and cellular transformation.International journal of molecular sciences · 2013Review
- Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes.Pharmacological reviews · 2012Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Our aim was to explore the involvement of the transcriptional suppressor GCF2 in silencing RhoA, disorganization of the cytoskeleton, mislocalization of MRP1, and sensitivity to anticancer agents as an upstream gene target in cancer therapy. Increased expression of GCF2 was found in human cisplatin-resistant cells, and overexpression in GCF2-transfected cells results in loss of RhoA expression and disruption of the actin/filamin network. In consequence, the membrane transporter MRP1 was internalized from the cell surface into the cytoplasm, rendering cells sensitive to doxorubicin by more than 10-fold due to increased accumulation of doxorubicin in the cells. The GCF2 transfectants also showed reduced accumulation of cisplatin and increased resistance. siRNA targeted to GCF2 suppressed the expression of GCF2 in cisplatin-resistant cells, reactivated RhoA expression, and restored the fine structure of actin microfilaments. MRP1 was also relocated to the cell surface. siRNA targeted to RhoA increased resistance 3-fold in KB-3-1 and KB-CP.5 cells. These data for the first time demonstrate a novel complex regulatory pathway downstream from GCF2 involving the small GTPase RhoA, actin/filamin dynamics, and membrane protein trafficking. This pathway mediates diverse responses to cytotoxic compounds, and also provides a molecular basis for further investigation into the pleiotropic resistance mechanism at play in cisplatin-resistant cells.
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