Transcription factor PRRX1-activated ANXA6 facilitates EGFR-PKCα complex formation and enhances cisplatin sensitivity in bladder cancer
- Jinlong Cao 1, Siyu Chen 1, Jirong Wang 1, Xinpeng Fan 1, Shanhui Liu 2, Xiaoran Li 1, Li Yang 1
- Jinlong Cao 1, Siyu Chen 1, Jirong Wang 1
- 1Department of Urology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730000, China; Gansu Province Clinical Research Center for Urology, Lanzhou 730000, China.
- 2Gansu Province Clinical Research Center for Urology, Lanzhou 730000, China.
- 0Department of Urology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730000, China; Gansu Province Clinical Research Center for Urology, Lanzhou 730000, China.
Related Experiment Videos
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.This study reveals ANXA6 enhances cisplatin sensitivity in bladder cancer by inhibiting the EGFR pathway. ANXA6 and PRRX1 offer new therapeutic targets to overcome cisplatin resistance.
Area Of Science
- Oncology
- Molecular Biology
- Cancer Research
Background
- Cisplatin resistance is a significant clinical challenge in bladder cancer (BC).
- The role of Annexin A6 (ANXA6) in cisplatin resistance is not well understood.
- This research investigates ANXA6's potential to improve cisplatin sensitivity.
Purpose Of The Study
- To elucidate the role of ANXA6 in modulating cisplatin sensitivity in bladder cancer.
- To identify the molecular mechanisms by which ANXA6 influences cisplatin response.
- To explore ANXA6 as a potential therapeutic target for overcoming cisplatin resistance.
Main Methods
- Bioinformatics and clinical specimen analysis to correlate ANXA6 expression with cisplatin treatment outcomes.
- In vitro assays (CCK-8, clone formation, ROS, apoptosis, comet assays) to assess ANXA6's effect on cisplatin sensitivity.
- Molecular techniques including mass spectrometry, immunofluorescence, co-immunoprecipitation, ChIP-PCR, and dual-luciferase assays to determine ANXA6's mechanism of action and PRRX1's regulatory role.
- In vivo xenograft models to evaluate the therapeutic impact of ANXA6.
Main Results
- ANXA6 expression significantly correlates with cisplatin sensitivity in bladder cancer.
- ANXA6 overexpression enhances cisplatin-induced cell death, DNA damage, and apoptosis, and re-sensitizes resistant cells.
- ANXA6 promotes PKCα/EGFR complex formation, inhibiting EGFR phosphorylation and downstream signaling (AKT, ERK1/2).
- PRRX1 acts as a transcription factor that upregulates ANXA6 expression, thereby enhancing cisplatin's cytotoxic effects.
Conclusions
- ANXA6 plays a crucial role in enhancing cisplatin sensitivity and overcoming resistance in bladder cancer.
- The identified mechanism involves ANXA6-mediated inhibition of the EGFR pathway.
- Both PRRX1 and ANXA6 represent promising therapeutic targets for improving clinical outcomes in cisplatin-resistant bladder cancer.
Related Experiment Videos
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
01:58
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
02:23
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...

