FBXL5 attenuates RhoGDI2-induced cisplatin resistance in gastric cancer cells.

Abstract

OBJECTIVE:

The hemerythrin-like domain of F-box and leucine-rich repeat protein 5 (FBXL5), an E3 ubiquitin ligase subunit, has critical roles in the regulation of cancer cells metastasis and chemoresistance by targeting diverse substrates for ubiquitin-mediated destruction.

MATERIALS AND METHODS:

Here, we report that FBXL5 interacts with Rho GDP dissociation inhibitor 2 (RhoGDI2) and attenuates RhoGDI2-induced cisplatin resistance in gastric cancer cells. By utilizing immunoprecipitation (IP) coupled with mass spectrometry assay, we found that FBXL5 regulated gastric cancers migration via cortactin destruction.

RESULTS:

Depletion of FBXL5 enhances cisplatin resistance of gastric cancer cells through Erk and p38 activation. However, FBXL5 did not affect the abundance and stability of RhoGDI2. Instead, FBXL5 was rapidly degraded in response to cisplatin treatment in RhoGDI2-overexpressing gastric cancer cells.

CONCLUSIONS:

Collectively, our data suggested the existence of a FBXL5-RhoGDI2 negative feedback loop in RhoGDI2-induced cisplatin resistance in gastric cancer cells, implicating FBXL5 as a novel and promising therapeutic target for RhoGDI2-induced cisplatin resistance gastric cancers.

• Authors: W-D Wu, M Wang, H-H Ding, Z-J Qiu
• Journal: European review for medical and pharmacological sciences (Eur Rev Med Pharmacol Sci) Vol. 20 Issue 12 Pg. 2551-7 (06 2016) ISSN: 2284-0729 [Electronic] Italy
• PMID: 27383304 (Publication Type: Journal Article)

Chemical References

• CTTN protein, human
• Cortactin
• F-Box Proteins
• FBXL5 protein, human
• rho Guanine Nucleotide Dissociation Inhibitor beta
• Ubiquitin-Protein Ligase Complexes
• Cisplatin

Topics

• Cisplatin (pharmacology)
• Cortactin (metabolism)
• Drug Interactions
• Drug Resistance, Neoplasm
• F-Box Proteins (metabolism)
• Humans
• Stomach Neoplasms (drug therapy, metabolism)
• Ubiquitin-Protein Ligase Complexes (metabolism)
• rho Guanine Nucleotide Dissociation Inhibitor beta (pharmacology)