Violacein switches off low molecular weight tyrosine phosphatase and rewires mitochondria in colorectal cancer cells.

Autor: Faria AVS; Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil., Fonseca EMB; Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil; Federal Institute of Education, Science and Technology of São Paulo (IFSP), São Roque, São Paulo, Brazil., Fernandes-Oliveira PS; Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil., de Lima TI; Department of Structural and Functional Biology, University of Campinas, (UNICAMP), Campinas, SP, Brazil., Clerici SP; Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil., Justo GZ; Department of Pharmaceutical Sciences and Department of Biochemistry, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil., Silveira LR; Department of Structural and Functional Biology, University of Campinas, (UNICAMP), Campinas, SP, Brazil., Durán N; Laboratory of Urogenital Carcinogenesis and Immunotherapy, Department of Structural and Functional Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil; Nanomedicine Research Unit (Nanomed), Center for Natural and Human Sciences (CCNH), Federal University of ABC (UFABC), Santo André, Brazil., Ferreira-Halder CV; Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil. Electronic address: carmenv@unicamp.br.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2022 Oct; Vol. 127, pp. 106000. Date of Electronic Publication: 2022 Jul 08.
DOI: 10.1016/j.bioorg.2022.106000
Abstrakt: In the last decade, emerging evidence has shown that low molecular weight protein tyrosine phosphatase (LMWPTP) not only contributes to the progression of cancer but is associated with prostate low survival rate and colorectal cancer metastasis. We report that LMWPTP favors the glycolytic profile in some tumors. Therefore, the focus of the present study was to identify metabolic enzymes that correlate with LMWPTP expression in patient samples. Exploratory data analysis from RNA-seq, proteomics, and histology staining, confirmed the higher expression of LMWPTP in CRC. Our descriptive statistical analyses indicate a positive expression correlation between LMWPTP and energy metabolism enzymes such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN). In addition, we examine the potential of violacein to reprogram energetic metabolism and LMWPTP activity. Violacein treatment induced a shift of glycolytic to oxidative metabolism associated with alteration in mitochondrial efficiency, as indicated by higher oxygen consumption rate. Particularly, violacein treated cells displayed higher proton leak and ATP-linked oxygen consumption rate (OCR) as an indicator of the OXPHOS preference. Notably, violacein is able to bind and inhibit LMWPTP. Since the LMWPTP acts as a hub of signaling pathways that offer tumor cells invasive advantages, such as survival and the ability to migrate, our findings highlight an unexplored potential of violacein in circumventing the metabolic plasticity of tumor cells.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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