Lipid-mediated regulation of epithelial-mesenchymal transition in colorectal cancer

Muzamil Ahmad Shah; Sharon Nagpal; S. Gokul Shankar; Antony V. Samrot; Alok Kumar Mishra

doi:10.1016/j.jpha.2025.101541

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Muzamil Ahmad Shah, Sharon Nagpal, S. Gokul Shankar, Antony V. Samrot, Alok Kumar Mishra. Lipid-mediated regulation of epithelial-mesenchymal transition in colorectal cancer[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101541

Citation:

Muzamil Ahmad Shah, Sharon Nagpal, S. Gokul Shankar, Antony V. Samrot, Alok Kumar Mishra. Lipid-mediated regulation of epithelial-mesenchymal transition in colorectal cancer[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101541

Citation:

Muzamil Ahmad Shah, Sharon Nagpal, S. Gokul Shankar, Antony V. Samrot, Alok Kumar Mishra. Lipid-mediated regulation of epithelial-mesenchymal transition in colorectal cancer[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101541

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Lipid-mediated regulation of epithelial-mesenchymal transition in colorectal cancer

doi: 10.1016/j.jpha.2025.101541

1. Department of Microbiology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India;
2. Department of Microbiology, Faculty of Medicine, Manipal University College, Persimpangan Batu Hampar, Bukit Baru, 75150 Melaka, Malaysia

Funds:

The authors would like to acknowledge Lovely Professional University (LPU), Phagwara, and Manipal University CollegeMalaysia for their support in conducting the study. The authors would like to acknowledge all the funding agencies involved.

Received Date: May 06, 2025
Accepted Date: Dec. 30, 2025
Rev Recd Date: Dec. 26, 2025
Available Online: Jan. 04, 2026

Abstract

Abstract

Colorectal cancer, being one of the leading cancers worldwide, is the cause of more than a million fatalities yearly. Notwithstanding breakthroughs in molecular comprehension and therapeutic approaches, the metastatic progression of colorectal cancer continues to pose a considerable threat. An essential occurrence in metastasis is the epithelial-mesenchymal transition (EMT), during which epithelial cells relinquish polarity and adhesion, acquiring a mesenchymal phenotype that augments motility and invasiveness. EMT is pivotal in cancer cell metastasis, stemness, drug resistance, and immune evasion. Recent studies have demonstrated a significant correlation between lipid metabolism and EMT in colorectal cancer. Modified lipid metabolism, characterized by enhanced fatty acid synthesis and elevated monounsaturated fatty acid (MUFA) generation, facilitates cancer cell motility. Enzymes such as stearoyl-CoA desaturase 1(SCD1) and Fatty acid synthase (FASN) serve as crucial regulators. Lipid molecules, including phosphatidylinositol (3,4,5)-trisphosphate (PIP3), affect signaling pathways like phosphoinositide 3-kinase/Ak strain transforming (PI3K/Akt), which also govern EMT. The gut microbiota influences colorectal cancer progression via dysbiosis, inflammation, and modified lipid metabolism, with short-chain fatty acids (SCFAs), especially butyrate, exhibiting anti-tumor properties. Focusing on lipid metabolic pathways, EMT regulators, and alternative splicing processes presents promising therapeutic approaches to impede colorectal cancer spread and surmount resistance to standard treatments. Understanding the intricate relationships among lipid metabolism, EMT, and the microbiota is essential for developing innovative therapeutics for colorectal cancer.
- Colorectal cancer,
- EMT,
- lipid metabolism,
- metastasis,
- short-chain fatty acids,
- transcription factors

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References(106)

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