Clinical and biochemical relevance of monounsaturated fatty acid metabolism targeting strategy for cancer stem cell elimination in colon cancer

SeokGyeong Choi; Young Ji Yoo; Hyejin Kim; Hani Lee; Hayung Chung; Myung-Hee Nam; Ju-Yeon Moon; Hye Suk Lee; Sukjoon Yoon; Woo-Young Kim

doi:10.1016/j.bbrc.2019.08.137

Clinical and biochemical relevance of monounsaturated fatty acid metabolism targeting strategy for cancer stem cell elimination in colon cancer

Biochem Biophys Res Commun. 2019 Oct 29;519(1):100-105. doi: 10.1016/j.bbrc.2019.08.137. Epub 2019 Aug 31.

Authors

Affiliations

¹ College of Pharmacy, Sookmyung Women's University, Seoul, 04312, South Korea.
² Environmental Risk and Welfare Research Team, Korea Basic Science Institute, Seoul, 02841, South Korea.
³ Drug Metabolism & Bioanalysis Laboratory, College of Pharmacy, The Catholic University of Korea, Bucheon, 14662, South Korea.
⁴ Research Institute of Women's Health, Sookmyung Women's University, Seoul, 04310, South Korea.
⁵ College of Pharmacy, Sookmyung Women's University, Seoul, 04312, South Korea; Research Institute of Pharmaceutical Sciences, Sookmyung Women's University, Seoul, 04312, South Korea. Electronic address: wykim@sookmyung.ac.kr.

PMID: 31481234
DOI: 10.1016/j.bbrc.2019.08.137

Abstract

Lipid metabolism is associated with colon cancer prognosis and incidence. Stearoyl-CoA desaturase 1 (SCD1), which converts fully saturated fatty acids (SFAs) to monounsaturated fatty acids (MUFAs), has been suggested as a vulnerable target for selective elimination of cancer stem cells (CSCs). However, the clinical significance and physiological role of SCD1 in CSCs has not been well demonstrated. Here, we showed the clinical and biochemical relevance of blocking SCD1 to target CSCs by analyzing human colon cancer data from TCGA and through lipidomic profiling of CSCs with or without SCD1 inhibition using mass spectrometry. Positive associations between SCD1 expression and colorectal cancer patient clinical status and the expression of CSC-related genes (WNT and NOTCH signaling) were found based on TCGA data analysis. Lipidomic profiling of CSCs and bulk cancer cells (BCCs) using mass spectrometry revealed that colon CSCs contained a distinctive lipid profile, with higher free MUFA and lower free SFA levels than in BCCs, suggesting that enhanced SCD1 activity generates MUFAs that may support WNT signaling in CSCs. In addition, all identified phosphatidyl-ethanolamine-containing MUFAs were found at higher levels in CSCs. Interestingly, we observed lower phosphatidyl-serine (18:1/18:0), phosphatidyl-choline (PC; p-18:0/18:1)), and sphingomyelin (SM; d18:1/20:0 or d16:1/22:0) levels in CSCs than in BCCs. Of those, SCD1 inhibition, which efficiently diminished free MUFA levels, increased those specific PC and SM and MUFAs in CSCs promptly. These results suggest that these specific lipid composition is critical for CSC stem cell maintenance. In addition, not only free MUFAs, which are known to be required for WNT signaling, but also other phospholipids, such as SM, which are important for lipid raft formation, may mediate other cell signaling pathways that support CSC maintenance. Comparison of the lipidomic profiles of colon cancer cells with those of previously reported for glioma cells further demonstrated the tissue specific characteristics of lipid metabolism in CSCs.

Keywords: Cancer stem cell; Lipidomics; Mono-unsaturated fatty acid; Stearoyl-CoA desaturase 1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Colonic Neoplasms / genetics
Colonic Neoplasms / metabolism*
Colonic Neoplasms / pathology*
Disease Progression
Fatty Acids, Monounsaturated / metabolism*
Gene Expression Regulation, Neoplastic
Humans
Lipid Metabolism
Neoplastic Stem Cells / metabolism*
Neoplastic Stem Cells / pathology
Phospholipids / metabolism
Signal Transduction
Stearoyl-CoA Desaturase / genetics
Stearoyl-CoA Desaturase / metabolism

Substances

Fatty Acids, Monounsaturated
Phospholipids
SCD1 protein, human
Stearoyl-CoA Desaturase