Search Results (2)

The endothelin-1 (ET1) peptide has a pathological role in the activation of proliferation, survival and invasiveness pathways in different cancers. ET1’s effects rely on its activation by the endothelin-converting enzyme-1 (ECE1), which is expressed as four isoforms, differing only in their cytoplasmic N-terminuses. We already demonstrated in colorectal cancer, glioblastoma, and preliminarily lung cancer, that the isoform ECE1c heightens aggressiveness by promoting cancer stem cell traits. This is achieved through a non-canonical ET1-independent mechanism of enhancement of ECE1c’s stability upon CK2-dependent phosphorylation at S18 and S20. Here, a K6 residue is presumably responsible for ECE1c ubiquitination as its mutation to R impairs proteasomal degradation. However, how phosphorylation enhances ECE1c’s stability and how this translates into aggressiveness are still open questions. In this brief report, by swapping residues to either phospho-mimetic or phospho-resistant amino acids, we propose that the N-terminus may also be phosphorylated at Y5 and/or T9 by an unknown kinase(s). In addition, N-terminus phosphorylation may lead to a blockage of K6 ubiquitination, increasing ECE1c’s stability and presumably activating the Wnt/β-catenin signaling pathway. Thus, a novel CK2/ECE1c partnership may be emerging to promote aggressiveness and thus become a biomarker of poor prognosis and a potential therapeutic target for several cancers. Full article

Colorectal cancer (CRC) has the fourth-highest incidence of all cancer types, and its incidence has steadily increased in the last decade. The general transcription factor III (GTF3) family, comprising GTF3A, GTF3B, GTF3C1, and GTFC2, were stated to be linked with the expansion of different types of cancers; however, their messenger (m)RNA expressions and prognostic values in colorectal cancer need to be further investigated. To study the transcriptomic expression levels of GTF3 gene members in colorectal cancer in both cancerous tissues and cell lines, we first performed high-throughput screening using the Oncomine, GEPIA, and CCLE databases. We then applied the Prognoscan database to query correlations of their mRNA expressions with the disease-specific survival (DSS), overall survival (OS), and disease-free survival (DFS) status of the colorectal cancer patient. Furthermore, proteomics expressions of GTF3 family members in clinical colorectal cancer specimens were also examined using the Human Protein Atlas. Finally, genomic alterations of GTF3 family gene expressions in colorectal cancer and their signal transduction pathways were studied using cBioPortal, ClueGO, CluePedia, and MetaCore platform. Our findings revealed that GTF3 family members’ expressions were significantly correlated with the cell cycle, oxidative stress, WNT/β-catenin signaling, Rho GTPases, and G-protein-coupled receptors (GPCRs). Clinically, high GTF3A and GTF3B expressions were significantly correlated with poor prognoses in colorectal cancer patients. Collectively, our study declares that GTF3A was overexpressed in cancer tissues and cell lines, particularly colorectal cancer, and it could possibly step in as a potential prognostic biomarker. Full article