Proteomic analysis of holocarboxylase synthetase deficient-MDA-MB-231 breast cancer cells revealed the biochemical changes associated with cell death, impaired growth signaling, and metabolism.

Autor:	Sukjoi W; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand., Young C; Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia., Acland M; Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia., Siritutsoontorn S; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand., Roytrakul S; Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology Agency, Pathumthani, Thailand., Klingler-Hoffmann M; Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia., Hoffmann P; Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia., Jitrapakdee S; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular biosciences [Front Mol Biosci] 2024 Jan 11; Vol. 10, pp. 1250423. Date of Electronic Publication: 2024 Jan 11 (Print Publication: 2023).
DOI:	10.3389/fmolb.2023.1250423
Abstrakt:	We have previously shown that the holocarboxylase synthetase (HLCS) is overexpressed in breast cancer tissue of patients, and silencing of its expression in triple-negative cancer cell line inhibits growth and migration. Here we investigated the global biochemical changes associated with HLCS knockdown in MDA-MB-231 cells to discern the pathways that involve HLCS. Proteomic analysis of two independent HLCS knockdown cell lines identified 347 differentially expressed proteins (DEPs) whose expression change > 2-fold ( p < 0.05) relative to the control cell line. GO enrichment analysis showed that these DEPs were mainly associated with the cellular process such as cellular metabolic process, cellular response to stimulus, and cellular component organization or biogenesis, metabolic process, biological regulation, response to stimuli, localization, and signaling. Among the 347 identified DEPs, 64 proteins were commonly found in both HLCS knockdown clones, confirming their authenticity. Validation of some of these DEPs by Western blot analysis showed that plasminogen activator inhibitor type 2 (SerpinB2) and interstitial collagenase (MMP1) were approximately 90% decreased in HLCS knockdown cells, consistent with a 50%-60% decrease in invasion ability of knockdown cells. Notably, argininosuccinate synthase 1 (ASS1), one of the enzymes in the urea cycle, showed approximately a 10-fold increase in the knockdown cells, suggesting the crucial role of HLCS in supporting the urea cycle in the triple-negative cancer cell line. Collectively, our proteomic data provide biochemical insights into how suppression of HLCS expression perturbs global changes in cellular processes and metabolic pathways, impairing cell growth and invasion. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Sukjoi, Young, Acland, Siritutsoontorn, Roytrakul, Klingler-Hoffmann, Hoffmann and Jitrapakdee.)
Databáze:	MEDLINE
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