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

Author(s)

Faria, Alessandra V. S. ; Fonseca, Emanuella M. B. ; Fernandes-Oliveira, Patricia de S. ; de Lima, Tanes I. ; Clerici, Stefano P. ; Justo, Giselle Z. ; Silveira, Leonardo R. ; Duran, Nelson ; Ferreira-Halder, Carmen, V

• Document type: Journal article
• Source: BIOORGANIC CHEMISTRY; v. 127, p. 9-pg., 2022-07-16.

Abstract

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. (AU)

• FAPESP's process: 17/08119-8 - Hematogenous tumor metastasis in colon rectal cancer cells: influence of LMWPTP and 3-bromopyruvate
• Grantee: Alessandra Valéria de Sousa Faria
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/04409-4 - Gastric cancer spheroids and organoids: protein kinases and extracellular matrix architecture tracking and therapeutic impact
• Grantee: Carmen Veríssima Ferreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/20412-7 - Low molecular weight protein tyrosine phosphatase in colorectal cancer: from the bench to product generation
• Grantee: Carmen Veríssima Ferreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/11433-0 - 3-bromopyruvate as molecular tool to uncover the biological basis of protein phosphatase LMWPTP contribution to leukemic cells resistance
• Grantee: Emanuella Maria Barreto Fonseca
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/03593-6 - Tumor-educated platelets and metastasis: relevance of LMWPTP and extracellular vesicles in Colorectal Cancer
• Grantee: Stefano Piatto Clerici
• Support Opportunities: Scholarships in Brazil - Doctorate