Cytosolic N-terminal formyl-methionine deformylation derives cancer stem cell features and tumor progression

• Published in: Scientific reports Vol. 14; no. 1; pp. 14900 - 9
• Main Authors: Kim, Dasom, Lee, Jongeun, Seok, Ok-Hee, Lee, Yoontae, Hwang, Cheol-Sang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 28.06.2024; Nature Portfolio
• Subjects: Antibodies; Bacteria; Cancer therapies; Cell growth; Cell proliferation; Cell self-renewal; Cell size; Cell surface; Colorectal cancer; Colorectal carcinoma; Cytosol; E coli; Life sciences; Methionine; Mitochondria; Peptide deformylase; Pluripotency; Polypeptides; Protein synthesis; Proteins; Stem cells; Surface markers; Tumorigenesis; Tumorigenicity; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-65701-1

Abstract Eukaryotic cells can synthesize formyl-methionine (fMet)-containing proteins not only in mitochondria but also in the cytosol to some extent. Our previous study revealed substantial upregulation of N-terminal (Nt)-fMet-containing proteins in the cytosol of SW480 colorectal cancer cells. However, the functional and pathophysiological implications remain unclear. Here, we demonstrated that removal of the Nt-formyl moiety of Nt-fMet-containing proteins (via expressing Escherichia coli PDF peptide deformylase) resulted in a dramatic increase in the proliferation of SW480 colorectal cancer cells. This proliferation coincided with the acquisition of cancer stem cell features, including reduced cell size, enhanced self-renewal capacity, and elevated levels of the cancer stem cell surface marker CD24 and pluripotent transcription factor SOX2. Furthermore, deformylation of Nt-fMet-containing proteins promoted the tumorigenicity of SW480 colorectal cancer cells in an in vivo xenograft mouse model. Taken together, these findings suggest that cytosolic deformylation has a tumor-enhancing effect, highlighting its therapeutic potential for cancer treatment.