Nuclear magnetic resonance spectroscopy reveals dysregulation of monounsaturated fatty acid metabolism upon SPINK1 attenuation in colorectal cancer

• Published in: NMR in biomedicine 2022-07, Vol.35 (7), p.e4705-n/a
• Main Authors: Nigam, Shivansh, Ranjan, Renuka, Sinha, Neeraj, Ateeq, Bushra
• Format: Article
• Language: English
• Subjects: 1H NMR; Biological products; Cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - pathology; Deposition; Droplets; Fatty acids; Fatty Acids, Monounsaturated; Humans; Inflammation; Inflammatory response; Lecithin; Lipid Metabolism; Lipids; Magnetic Resonance Spectroscopy; Metabolism; MUFA; NMR; NMR spectroscopy; Nuclear magnetic resonance; Phosphatidylcholine; Polyunsaturated fatty acids; Protease inhibitors; Proteinase inhibitors; Spectroscopy; Spectrum analysis; SPINK1; Triglycerides; Trypsin Inhibitor, Kazal Pancreatic - metabolism; Tumor cells
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.4705

Metabolic reprogramming, a key hallmark of cancer, plays a pivotal role in fulfilling the accelerated biological demands of tumor cells. Such metabolic changes trigger the production of several proinflammatory factors, thereby inciting cancer development and its progression. Serine protease inhibitor Kazal Type 1 (SPINK1), well known for its oncogenic role and its upregulation via acute‐phase reactions, is highly expressed in multiple cancers including colorectal cancer (CRC). Here, we show accumulation of lipid droplets in CRC cells stained with Oil Red O upon SPINK1 silencing. Furthermore, NMR spectroscopy analysis revealed an accretion of monounsaturated fatty acids (MUFAs) and phosphatidylcholine in these CRC cells, while the levels of polyunsaturated fatty acids remained unaltered. This alteration indicates the presence of MUFAs with the triglycerides in the lipid droplets as observed in SPINK1‐silenced CRC cells. Considering the role of MUFAs in the anti‐inflammatory response, our data hint that suppression of SPINK1 in CRC leads to activation of an anti‐inflammatory signaling milieu. Conclusively, our study uncovers a connection between lipid metabolism and SPINK1‐mediated CRC progression, hence paving the way for further exploration and better prognosis of SPINK1‐positive CRC patients. SPINK1 silencing in colorectal cancer cells revealed accumulation of lipid droplets with Oil Red O staining. 1H NMR spectroscopy revealed enhanced olefinic and other unsaturated fatty acid signals along with phosphatidylcholine, depicting enhanced monounsaturated fatty acid (MUFA) metabolism. Corroborating multivariate analysis data with our previously published global gene expression profiling data for SPINK1 silencing (GSE70761) confirmed the upregulation of genes regulating MUFA metabolism.