Research Advances in Lipid Metabolic Reprogramming Mechanisms of Colorectal Cancer Cells

Jin Meng; Yufeng Li; Jingwu Li

doi:10.71204/gbhp8s96

Authors

Jin Meng Graduate School of North China University of Science and Technology Author
Yufeng Li Hebei Key Laboratory of Molecular Oncology Author
Jingwu Li Tangshan People's Hospital Author

DOI:

https://doi.org/10.71204/gbhp8s96

Keywords:

Colorectal Cancer, Lipid Metabolism, Metabolic Reprogramming

Abstract

Colorectal cancer (CRC) is a highly aggressive form of cancer that poses a significant threat to public health worldwide. The progression of this disease is primarily driven by metabolic changes, especially the disruption of lipid metabolism. Cancerous CRC cells proliferate uncontrollably and invade surrounding tissues due to abnormal modifications in fatty acid synthesis, lipid uptake, storage, and β-oxidation. These metabolic shifts are influenced by key oncogenic signaling pathways, such as the PI3K/AKT/mTOR pathway and the MYC transcriptional network, which also enhance interactions with the tumor microenvironment's stromal elements. Recent research suggests that targeting lipid metabolism through pharmacological means could offer substantial clinical benefits. This article provides a comprehensive analysis of the molecular mechanisms involved in the reprogramming of lipid metabolism in CRC development and assesses its potential for innovative therapeutic approaches.

References

Ackerman, D., Tumanov, S., Qiu, B., Michalopoulou, E., Spata, M., Azzam, A., Xie, H., Simon, M. C., & Kamphorst, J. J. (2018). Triglycerides Promote Lipid Homeostasis during Hypoxic Stress by Balancing Fatty Acid Saturation. Cell Rep, 24(10), 2596-2605.

Andre, T., Elez, E., Van Cutsem, E., Jensen, L. H., Bennouna, J., Mendez, G., Schenker, M., de la Fouchardiere, C., Limon, M. L., Yoshino, T., Li, J., Lenz, H. J., Manzano Mozo, J. L., Tortora, G., Garcia-Carbonero, R., Dahan, L., Chalabi, M., Joshi, R., Goekkurt, E., . . . CheckMate, H. W. I. (2024). Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer. N Engl J Med, 391(21), 2014-2026.

Babaei-Jadidi, R., Kashfi, H., Alelwani, W., Karimi Bakhtiari, A., Kattan, S. W., Mansouri, O. A., Mukherjee, A., Lobo, D. N., & Nateri, A. S. (2022). Anti-miR-135/SPOCK1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids. Oncogenesis, 11(1), 4.

Barnell, E. K., Wurtzler, E. M., & Lieberman, J. L. R. F. P. H. K. L. H. A. (2023). Multitarget Stool RNA Test for Colorectal Cancer Screening. JAMA: the Journal of the American Medical Association, 330(18), 1760-1768.

Cao, Q., Tian, Y., Deng, Z., Yang, F., & Chen, E. (2024). Epigenetic alteration in colorectal cancer: potential diagnostic and prognostic implications. International Journal of Molecular Sciences, 25(6), 3358.

Capece, D., D’Andrea, D., Begalli, F., Goracci, L., Tornatore, L., Alexander, J. L., ... & Franzoso, G. (2021). Enhanced triacylglycerol catabolism by carboxylesterase 1 promotes aggressive colorectal carcinoma. The Journal of clinical investigation, 131(11), e137845.

Chen, D., Zhou, X., Yan, P., Yang, C., Li, Y., Han, L., & Ren, X. (2023). Lipid metabolism reprogramming in colorectal cancer. J Cell Biochem, 124(1), 3-16.

Chen, J., Ye, J., & Lai, R. (2023). A lipid metabolism-related gene signature reveals dynamic immune infiltration of the colorectal adenoma-carcinoma sequence. Lipids Health Dis, 22(1), 92.

Chen, X., Ma, Z., Yi, Z., Wu, E., Shang, Z., Tuo, B., Li, T., & Liu, X. (2024). The effects of metabolism on the immune microenvironment in colorectal cancer. Cell Death Discov, 10(1), 118.

Chen, Y., Liang, Z., & Lai, M. (2024). Targeting the devil: Strategies against cancer-associated fibroblasts in colorectal cancer. Transl Res, 270, 81-93.

Chen, Y., Liao, X., Li, Y., Cao, H., Zhang, F., Fei, B., Bao, C., Cao, H., Mao, Y., & Chen, X. P. (2023). Effects of prebiotic supplement on gut microbiota, drug bioavailability, and adverse effects in patients with colorectal cancer at different primary tumor locations receiving chemotherapy: study protocol for a randomized clinical trial. Trials, 24.

Cheng, C. T., Lai, J. M., Chang, P. M., Hong, Y. R., Huang, C. F., & Wang, F. S. (2023). Identifying essential genes in genome-scale metabolic models of consensus molecular subtypes of colorectal cancer. PLoS One, 18(5), e0286032.

Cheng, H., Sun, Y., Yu, X., Zhou, D., Ding, J., Wang, S., & Ma, F. (2023). FASN promotes gallbladder cancer progression and reduces cancer cell sensitivity to gemcitabine through PI3K/AKT signaling. Drug discoveries & therapeutics, 17(5), 328-339.

Čipak Gašparović, A., Milković, L., Rodrigues, C., Mlinarić, M., & Soveral, G. (2021). Peroxiporins Are Induced upon Oxidative Stress Insult and Are Associated with Oxidative Stress Resistance in Colon Cancer Cell Lines. Antioxidants (Basel), 10(11), 1856.

Cotte, A. K., Aires, V., Ghiringhelli, F., & Delmas, D. (2018). LPCAT2 controls chemoresistance in colorectal cancer. Mol Cell Oncol, 5(3), e1448245.

Courneya, K. S., Vardy, J. L., O'Callaghan, C. J., Gill, S., Friedenreich, C. M., Wong, R. K. S., Dhillon, H. M., Coyle, V., Chua, N. S., Jonker, D. J., Beale, P. J., Haider, K., Tang, P. A., Bonaventura, T., Wong, R., Lim, H. J., Burge, M. E., Hubay, S., Sanatani, M., . . . Booth, C. M. (2025). Structured Exercise after Adjuvant Chemotherapy for Colon Cancer. N Engl J Med, 393(1), 13-25.

Criscuolo, D., Avolio, R., Calice, G., Laezza, C., Paladino, S., Navarra, G., Maddalena, F., Crispo, F., Pagano, C., Bifulco, M., Landriscina, M., Matassa, D. S., & Esposito, F. (2020). Cholesterol Homeostasis Modulates Platinum Sensitivity in Human Ovarian Cancer. Cells, 9(4), 828.

Dai, W., Liu, Y., Zhang, T., Huang, Z., Xu, X., Zhao, Z., Liu, J., Zhai, E., Cai, S., & Chen, J. (2023). Spindle function and Wnt pathway inhibition by PBX1 to suppress tumor progression via downregulating DCDC2 in colorectal cancer. Oncogenesis, 12(1), 3.

Deng, S., Cheng, D., Wang, J., Gu, J., Xue, Y., Jiang, Z., Qin, L., Mao, F., Cao, Y., & Cai, K. (2023). MYL9 expressed in cancer-associated fibroblasts regulate the immune microenvironment of colorectal cancer and promotes tumor progression in an autocrine manner. J Exp Clin Cancer Res, 42(1), 294.

Diao, X. Y., & Lin, T. (2019). Progress in therapeutic strategies based on cancer lipid metabolism. Thorac Cancer, 10(9), 1741-1743.

Dobre, M., Trandafir, B., Milanesi, E., Salvi, A., Bucuroiu, I. A., Vasilescu, C., Niculae, A. M., Herlea, V., Hinescu, M. E., & Constantinescu, G. (2022). Molecular profile of the NF-kappaB signalling pathway in human colorectal cancer. J Cell Mol Med, 26(24), 5966-5975.

Du, Y., Rokavec, M., & Hermeking, H. (2023). Squalene epoxidase/SQLE is a candidate target for treatment of colorectal cancers with p53 mutation and elevated c-MYC expression. Int J Biol Sci, 19(13), 4103-4122.

Elez, E., Yoshino, T., Shen, L., Lonardi, S., Van Cutsem, E., Eng, C., Kim, T. W., Wasan, H. S., Desai, J., Ciardiello, F., Yaeger, R., Maughan, T. S., Morris, V. K., Wu, C., Usari, T., Laliberte, R., Dychter, S. S., Zhang, X., Tabernero, J., . . . Investigators, B. T. (2025). Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated Colorectal Cancer. N Engl J Med, 392(24), 2425-2437.

Fowler, J. W. M., Boutagy, N. E., Zhang, R., Horikami, D., Whalen, M. B., Romanoski, C. E., & Sessa, W. C. (2023). SREBP2 regulates the endothelial response to cytokines via direct transcriptional activation of KLF6. J Lipid Res, 64(8), 100411.

Gao, Y., Nan, X., Shi, X., Mu, X., Liu, B., Zhu, H., Yao, B., Liu, X., Yang, T., Hu, Y., & Liu, S. (2019). SREBP1 promotes the invasion of colorectal cancer accompanied upregulation of MMP7 expression and NF-kappaB pathway activation. BMC Cancer, 19(1), 685.

Gao, Y., Zhao, Q., Mu, X., Zhu, H., Liu, B., Yao, B., Liu, X., Xue, W., Wang, B., & Liu, S. (2019). SREBP1 promotes 5-FU resistance in colorectal cancer cells by inhibiting the expression of caspase7. Int J Clin Exp Pathol, 12(3), 1095-1100.

Gomes, S., Rodrigues, A. C., Pazienza, V., & Preto, A. (2023). Modulation of the tumor microenvironment by microbiota-derived short-chain fatty acids: impact in colorectal cancer therapy. International Journal of Molecular Sciences, 24(6), 5069.

Gong, J., Lin, Y., Zhang, H., Liu, C., Cheng, Z., Yang, X., Zhang, J., Xiao, Y., Sang, N., Qian, X., Wang, L., Cen, X., Du, X., & Zhao, Y. (2020). Reprogramming of lipid metabolism in cancer-associated fibroblasts potentiates migration of colorectal cancer cells. Cell Death Dis, 11(4), 267.

Gonzalez-Fernandez, M. J., Ortea, I., & Guil-Guerrero, J. L. (2020). alpha-Linolenic and gamma-linolenic acids exercise differential antitumor effects on HT-29 human colorectal cancer cells. Toxicol Res (Camb), 9(4), 474-483.

Guo, C., Zhang, L., Zhao, M., Ai, Y., Liao, W., Wan, L., Liu, Q., Li, S., Zeng, J., Ma, X., & Tang, J. (2023). Targeting lipid metabolism with natural products: A novel strategy for gastrointestinal cancer therapy. Phytother Res, 37(5), 2036-2050.

Han, L., Dai, W., Luo, W., Ye, L., Fang, H., Mo, S., Li, Q., Xu, Y., Wang, R., & Cai, G. (2023). Enhanced De Novo Lipid Synthesis Mediated by FASN Induces Chemoresistance in Colorectal Cancer. Cancers (Basel), 15(3), 562.

Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646-674.

Ikeda, T., Katoh, Y., Hino, H., Seta, D., Ogawa, T., Iwata, T., Nishio, H., Sugawara, M., & Hirai, S. (2024). FADS2 confers SCD1 inhibition resistance to cancer cells by modulating the ER stress response. Sci Rep, 14(1), 13116.

Jin, H., Zhu, M., Zhang, D., Liu, X., Guo, Y., Xia, L., Chen, Y., Chen, Y., Xu, R., Liu, C., Xi, Q., Xia, S., Shi, T., & Zhang, G. (2023). B7H3 increases ferroptosis resistance by inhibiting cholesterol metabolism in colorectal cancer. Cancer Sci, 114(11), 4225-4236.

Jones, D. T., Valli, A., Haider, S., Zhang, Q., Smethurst, E. A., Schug, Z. T., Peck, B., Aboagye, E. O., Critchlow, S. E., Schulze, A., Gottlieb, E., Wakelam, M. J. O., & Harris, A. L. (2019). 3D Growth of Cancer Cells Elicits Sensitivity to Kinase Inhibitors but Not Lipid Metabolism Modifiers. Mol Cancer Ther, 18(2), 376-388.

Kakimoto, M., Yamamoto, H., & Tanaka, A. R. (2020). Spermine synthesis inhibitor blocks 25-hydroxycholesterol-induced- apoptosis via SREBP2 upregulation in DLD-1 cell spheroids. Biochem Biophys Rep, 22, 100754.

Kibriya, M. G., Jasmine, F., Pekow, J., Munoz, A., Weber, C., Raza, M., Kamal, M., Ahsan, H., & Bissonnette, M. (2023). Pathways Related to Colon Inflammation Are Associated with Colorectal Carcinoma: A Transcriptome- and Methylome-Wide Study. Cancers (Basel), 15(11), 2921.

Koncina, E., Nurmik, M., Pozdeev, V. I., Gilson, C., Tsenkova, M., Begaj, R., Stang, S., Gaigneaux, A., Weindorfer, C., Rodriguez, F., Schmoetten, M., Klein, E., Karta, J., Atanasova, V. S., Grzyb, K., Ullmann, P., Halder, R., Hengstschlager, M., Graas, J., . . . Letellier, E. (2023). IL1R1(+) cancer-associated fibroblasts drive tumor development and immunosuppression in colorectal cancer. Nat Commun, 14(1), 4251.

Kopetz, S., Murphy, D. A., Pu, J., Ciardiello, F., Desai, J., Van Cutsem, E., Wasan, H. S., Yoshino, T., Saffari, H., Zhang, X., Hamilton, P., Xie, T., Yaeger, R., & Tabernero, J. (2024). Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial. Nat Med, 30(11), 3261-3271.

Li, C., Wang, Y., Liu, D., Wong, C. C., Coker, O. O., Zhang, X., Liu, C., Zhou, Y., Liu, Y., Kang, W., To, K. F., Sung, J. J., & Yu, J. (2022). Squalene epoxidase drives cancer cell proliferation and promotes gut dysbiosis to accelerate colorectal carcinogenesis. Gut, 71(11), 2253-2265.

Li, Q., Wang, Y., Wu, S., Zhou, Z., Ding, X., Shi, R., Thorne, R. F., Zhang, X. D., Hu, W., & Wu, M. (2019). CircACC1 Regulates Assembly and Activation of AMPK Complex under Metabolic Stress. Cell Metab, 30(1), 157-173 e157.

Li, W., Zong, S., Shi, Q., Li, H., Xu, J., & Hou, F. (2016). Hypoxia-induced vasculogenic mimicry formation in human colorectal cancer cells: Involvement of HIF-1a, Claudin-4, and E-cadherin and Vimentin. Sci Rep, 6, 37534.

Liao, L., Zhang, F., Zhuo, Z., Huang, C., Zhang, X., Liu, R., Gao, B., & Ding, S. (2023). Regulation of Fatty Acid Metabolism and Inhibition of Colorectal Cancer Progression by Erchen Decoction. Evid Based Complement Alternat Med, 2023, 9557720.

Lin, J. R., Wang, S., Coy, S., Chen, Y. A., Yapp, C., Tyler, M., Nariya, M. K., Heiser, C. N., Lau, K. S., Santagata, S., & Sorger, P. K. (2023). Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer. Cell, 186(2), 363-381 e319.

Liu, J., Mi, J., & Zhou, B. P. (2016). Metabolic rewiring in cancer-associated fibroblasts provides a niche for oncogenesis and metastatic dissemination. Mol Cell Oncol, 3(1), e1056331.

Liu, L., Mo, M., Chen, X., Chao, D., Zhang, Y., Chen, X., Wang, Y., Zhang, N., He, N., Yuan, X., Chen, H., & Yang, J. (2023). Targeting inhibition of prognosis-related lipid metabolism genes including CYP19A1 enhances immunotherapeutic response in colon cancer. J Exp Clin Cancer Res, 42(1), 85.

Liu, L., Xiao, N., & Liang, J. (2023). Comparative efficacy of oral drugs for chronic radiation proctitis - a systematic review. Syst Rev, 12(1), 146.

Liu, X., Qin, J., Nie, J., Gao, R., Hu, S., Sun, H., Wang, S., & Pan, Y. (2023). ANGPTL2+cancer-associated fibroblasts and SPP1+macrophages are metastasis accelerators of colorectal cancer. Front Immunol, 14, 1185208.

Liu, X., Zhang, P., Xu, J., Lv, G., & Li, Y. (2022). Lipid metabolism in tumor microenvironment: novel therapeutic targets. Cancer Cell Int, 22(1), 224.

Liu, Y., Hua, W., Li, Y., Xian, X., Zhao, Z., Liu, C., Zou, J., Li, J., Fang, X., & Zhu, Y. (2020). Berberine suppresses colon cancer cell proliferation by inhibiting the SCAP/SREBP-1 signaling pathway-mediated lipogenesis. Biochem Pharmacol, 174, 113776.

Lu, D., Li, X., Yuan, Y., Li, Y., Wang, J., Zhang, Q., Yang, Z., Gao, S., Zhang, X., & Zhou, B. (2023). Integrating TCGA and single-cell sequencing data for colorectal cancer: a 10-gene prognostic risk assessment model. Discov Oncol, 14(1), 168.

Lu, T., Sun, L., Wang, Z., Zhang, Y., He, Z., & Xu, C. (2019). Fatty acid synthase enhances colorectal cancer cell proliferation and metastasis via regulating AMPK/mTOR pathway. Onco Targets Ther, 12, 3339-3347.

Markl, B., Reitsam, N. G., Grochowski, P., Waidhauser, J., & Grosser, B. (2024). The SARIFA biomarker in the context of basic research of lipid-driven cancers. NPJ Precis Oncol, 8(1), 165.

Markowska, A., Antoszczak, M., Markowska, J., & Huczyński, A. (2020). Statins: HMG-CoA Reductase Inhibitors as Potential Anticancer Agents against Malignant Neoplasms in Women. Pharmaceuticals (Basel), 13(12), 422.

Mehdizadeh, A., Bonyadi, M., Darabi, M., Rahbarghazi, R., Montazersaheb, S., Velaei, K., Shaaker, M., & Somi, M. H. (2017). Common chemotherapeutic agents modulate fatty acid distribution in human hepatocellular carcinoma and colorectal cancer cells. Bioimpacts, 7(1), 31-39.

Mika, A., Kobiela, J., Pakiet, A., Czumaj, A., Sokolowska, E., Makarewicz, W., Chmielewski, M., Stepnowski, P., Marino-Gammazza, A., & Sledzinski, T. (2020). Preferential uptake of polyunsaturated fatty acids by colorectal cancer cells. Sci Rep, 10(1), 1954.

Ming-Bin, G., Ya-Nan, W., Yong-Ting, X., Min, Z., Hao, T., Lian-Ping, Q., & Feng, G. (2023). TCM syndrome differentiation in colorectal cancer patients assisted by differences in gut microbiota: An exploratory study. Heliyon, 9(11), e21057.

Monirujjaman, M., Bathe, O. F., & Mazurak, V. C. (2022). Dietary EPA+DHA Mitigate Hepatic Toxicity and Modify the Oxylipin Profile in an Animal Model of Colorectal Cancer Treated with Chemotherapy. Cancers (Basel), 14(22), 5703.

Monirujjaman, M., Renani, L. B., Isesele, P., Dunichand-Hoedl, A. R., & Mazurak, V. C. (2023). Increased expression of hepatic stearoyl-CoA desaturase (SCD)-1 and depletion of eicosapentaenoic acid (EPA) content following cytotoxic cancer therapy are reversed by dietary fish oil. International Journal of Molecular Sciences, 24(4), 3547.

Montero-Calle, A., Gomez de Cedron, M., Quijada-Freire, A., Solis-Fernandez, G., Lopez-Alonso, V., Espinosa-Salinas, I., Pelaez-Garcia, A., Fernandez-Acenero, M. J., Ramirez de Molina, A., & Barderas, R. (2022). Metabolic Reprogramming Helps to Define Different Metastatic Tropisms in Colorectal Cancer. Front Oncol, 12, 903033.

Neil, E., Hennessey, R. C., Agorku, D., Park, D., Femel, J., Dibuono, M., Lafayette, H., Lloyd, E., Lo, H., & Makrigiorgos, A. (2024). Abstract 5565: Multiomic characterization of colorectal cancer using MICS technology reveals interaction of antigen presenting cancer associated fibroblasts and T cells. Cancer research, 84(6-Sup), 9.

Notarnicola, M., Caruso, M. G., Tutino, V., De Nunzio, V., Gigante, I., De Leonardis, G., Veronese, N., Rotolo, O., Reddavide, R., Stasi, E., Miraglia, C., Nouvenne, A., Meschi, T., De' Angelis, G. L., Di Mario, F., & Leandro, G. (2018). Nutrition and lipidomic profile in colorectal cancers. Acta Biomed, 89(9-S), 87-96.

Ogretmen, B. (2018). Sphingolipid metabolism in cancer signalling and therapy. Nat Rev Cancer, 18(1), 33-50.

Pakiet, A., Kobiela, J., Stepnowski, P., Sledzinski, T., & Mika, A. (2019). Changes in lipids composition and metabolism in colorectal cancer: a review. Lipids Health Dis, 18(1), 29.

Peng, S., Li, Y., Huang, M., Tang, G., Xie, Y., Chen, D., Hu, Y., Yu, T., Cai, J., Yuan, Z., Wang, H., Wang, H., Luo, Y., & Liu, X. (2022). Metabolomics reveals that CAF-derived lipids promote colorectal cancer peritoneal metastasis by enhancing membrane fluidity. Int J Biol Sci, 18(5), 1912-1932.

Perucha, E., Melchiotti, R., Bibby, J. A., Wu, W., Frederiksen, K. S., Roberts, C. A., Hall, Z., LeFriec, G., Robertson, K. A., Lavender, P., Gerwien, J. G., Taams, L. S., Griffin, J. L., de Rinaldis, E., van Baarsen, L. G. M., Kemper, C., Ghazal, P., & Cope, A. P. (2019). The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells. Nat Commun, 10(1), 498.

Qiu, Y. Y., Hu, S. J., Bao, Y. J., Liang, B., Yan, C. N., Shi, X. J., Yu, H., Zou, Y., Tang, L. R., Tang, Q. F., Feng, W., & Yin, P. H. (2015). Anti-angiogenic and anti-proliferative effects of inhibition of HIF-1alpha by p-HIF-1alpha RNAi in colorectal cancer. Int J Clin Exp Pathol, 8(7), 7913-7920.

Rashid, M. M., Lee, H., & Jung, B. H. (2020). Evaluation of the antitumor effects of PP242 in a colon cancer xenograft mouse model using comprehensive metabolomics and lipidomics. Sci Rep, 10(1), 17523.

Reitsam, N. G., Grosser, B., Enke, J. S., Mueller, W., Westwood, A., West, N. P., Quirke, P., Markl, B., & Grabsch, H. I. (2024). Stroma AReactive Invasion Front Areas (SARIFA): a novel histopathologic biomarker in colorectal cancer patients and its association with the luminal tumour proportion. Transl Oncol, 44, 101913.

Reitsam, N. G., Grozdanov, V., Loffler, C. M. L., Muti, H. S., Grosser, B., Kather, J. N., & Markl, B. (2024). Novel biomarker SARIFA in colorectal cancer: highly prognostic, not genetically driven and histologic indicator of a distinct tumor biology. Cancer Gene Ther, 31(2), 207-216.

Reitsam, N. G., Markl, B., Dintner, S., Sipos, E., Grochowski, P., Grosser, B., Sommer, F., Eser, S., Nerlinger, P., Jordan, F., Rank, A., Lohr, P., & Waidhauser, J. (2023). Alterations in Natural Killer Cells in Colorectal Cancer Patients with Stroma AReactive Invasion Front Areas (SARIFA). Cancers (Basel), 15(3), 994.

Ricoult, S. J. H., Yecies, J. L., Ben-Sahra, I., & Manning, B. D. (2015). Oncogenic PI3K and K-Ras stimulate de novo lipid synthesis through mTORC1 and SREBP. Oncogene.

Sampaio-Ribeiro, G., Ruivo, A., Silva, A., Santos, A. L., Oliveira, R. C., Gama, J., Cipriano, M. A., Tralhao, J. G., & Paiva, A. (2023). Innate Immune Cells in the Tumor Microenvironment of Liver Metastasis from Colorectal Cancer: Contribution to a Comprehensive Therapy. Cancers (Basel), 15(12), 3222.

Shan, J., Li, X., Sun, R., Yao, Y., Sun, Y., Kuang, Q., Dai, X., & Sun, Y. (2024). Palmitoyltransferase ZDHHC6 promotes colon tumorigenesis by targeting PPARgamma-driven lipid biosynthesis via regulating lipidome metabolic reprogramming. J Exp Clin Cancer Res, 43(1), 227.

Shen, C., Liu, J., Liu, H., Li, G., Wang, H., Tian, H., Mao, Y., & Hua, D. (2024). Timosaponin AIII induces lipid peroxidation and ferroptosis by enhancing Rab7-mediated lipophagy in colorectal cancer cells. Phytomedicine, 122, 155079.

Shi, B., Chen, J., Guo, H., Shi, X., Tai, Q., Chen, G., Yao, H., Mi, X., Zhong, R., Lu, Y., Zhao, Y., Sun, L., Zhou, D., Yao, Y., & He, S. (2025). ACOX1 activates autophagy via the ROS/mTOR pathway to suppress proliferation and migration of colorectal cancer. Sci Rep, 15(1), 2992.

Song, J., Park, S., Oh, J., Kim, D., Ryu, J. H., Park, W. C., Baek, I. J., Cheng, X., Lu, X., & Jin, E. J. (2020). NUDT7 Loss Promotes Kras(G12D) CRC Development. Cancers (Basel), 12(3), 576.

Sun, J., Jia, H., Bao, X., Wu, Y., Zhu, T., Li, R., & Zhao, H. (2021). Tumor exosome promotes Th17 cell differentiation by transmitting the lncRNA CRNDE-h in colorectal cancer. Cell Death Dis, 12(1), 123.

Tam, S. Y., Islam Khan, M. Z., Chen, J. Y., Yip, J. H. Y., Yan, H. Y., Tam, T. Y., & Law, H. K. W. (2023). Proteomic profiling of chemotherapy responses in FOLFOX-resistant colorectal cancer cells. International journal of molecular sciences, 24(12), 9899.

Terado, T., Kim, C. J., Ushio, A., Minami, K., Tambe, Y., Kageyama, S., Kawauchi, A., Tsunoda, T., Shirasawa, S., Tanaka, H., & Inoue, H. (2022). Cryptotanshinone suppresses tumorigenesis by inhibiting lipogenesis and promoting reactive oxygen species production in KRAS‑activated pancreatic cancer cells. Int J Oncol, 61(3), 108.

Valente, R., Cordeiro, S., Luz, A., Melo, M. C., Rodrigues, C. R., Baptista, P. V., & Fernandes, A. R. (2023). Doxorubicin-sensitive and -resistant colorectal cancer spheroid models: assessing tumor microenvironment features for therapeutic modulation. Front Cell Dev Biol, 11, 1310397.

Wang, J., Millstein, J., Yang, Y., Stintzing, S., Arai, H., Battaglin, F., Kawanishi, N., Soni, S., Zhang, W., Mancao, C., Cremolini, C., Liu, T., Heinemann, V., Falcone, A., Shen, L., & Lenz, H. J. (2023). Impact of genetic variants involved in the lipid metabolism pathway on progression free survival in patients receiving bevacizumab-based chemotherapy in metastatic colorectal cancer: a retrospective analysis of FIRE-3 and MAVERICC trials. EClinicalMedicine, 57, 101827.

Wang, X., Qu, Y., Ji, J., Liu, H., Luo, H., Li, J., & Han, X. (2024). Colorectal cancer cells establish metabolic reprogramming with cancer-associated fibroblasts (CAFs) through lactate shuttle to enhance invasion, migration, and angiogenesis. Int Immunopharmacol, 143(Pt 2), 113470.

Wang, X., Zhu, Y., Zhou, H., Huang, Z., Chen, H., Zhang, J., Yang, S., Chen, G., & Zhang, Q. (2023). [Integrated analysis of serum untargeted metabolomics and targeted bile acid metabolomics for identification of diagnostic biomarkers for colorectal cancer]. Nan Fang Yi Ke Da Xue Xue Bao, 43(3), 443-453.

Wang, Y., Hinz, S., Uckermann, O., Honscheid, P., von Schonfels, W., Burmeister, G., Hendricks, A., Ackerman, J. M., Baretton, G. B., Hampe, J., Brosch, M., Schafmayer, C., Shevchenko, A., & Zeissig, S. (2020). Shotgun lipidomics-based characterization of the landscape of lipid metabolism in colorectal cancer. Biochim Biophys Acta Mol Cell Biol Lipids, 1865(3), 158579.

Wang, Y., Xu, C., Yang, X., Liu, X., Guo, Z., Lin, X., Li, L., & Huang, Z. (2024). Glycerol-3-phosphate acyltransferase 3-mediated lipid droplets accumulation confers chemoresistance of colorectal cancer. MedComm (2020), 5(2), e486.

Wen, Y. A., Xiong, X., Zaytseva, Y. Y., Napier, D. L., Vallee, E., Li, A. T., Wang, C., Weiss, H. L., Evers, B. M., & Gao, T. (2018). Downregulation of SREBP inhibits tumor growth and initiation by altering cellular metabolism in colon cancer. Cell Death Dis, 9(3), 265.

Wu, S., Zhu, D., Feng, H., Li, Y., Zhou, J., Li, Y., & Hou, T. (2023). Comprehensive analysis of HOXC8 associated with tumor microenvironment characteristics in colorectal cancer. Heliyon, 9(11), e21346.

Yan, L., Zheng, J., Wang, Q., & Hao, H. (2023). Role of cancer-associated fibroblasts in colorectal cancer and their potential as therapeutic targets. Biochem Biophys Res Commun, 681, 127-135.

Yan, Y., Yang, Y., Ning, C., Wu, N., Yan, S., & Sun, L. (2023). Role of Traditional Chinese Medicine Syndrome Type, Gut Microbiome, and Host Immunity in Predicting Early and Advanced Stage Colorectal Cancer. Integr Cancer Ther, 22, 15347354221144051.

Yang, C., Huang, S., Cao, F., & Zheng, Y. (2021). A lipid metabolism-related genes prognosis biomarker associated with the tumor immune microenvironment in colorectal carcinoma. BMC Cancer, 21(1), 1182.

Yang, K., Li, H., Dong, J., Dong, Y., & Wang, C. Z. (2015). Expression profile of polyunsaturated fatty acids in colorectal cancer. World J Gastroenterol, 21(8), 2405-2412.

Yao, J., Song, Y., Yu, X., & Lin, Z. (2023). Interaction between N(6)-methyladenosine modification and the tumor microenvironment in colorectal cancer. Mol Med, 29(1), 129.

Ye, M., Hu, C., Chen, T., Yu, P., Chen, J., Lu, F., Xu, L., Zhong, Y., Yan, L., Kan, J., Bai, J., Li, X., Tian, Y., & Tang, Q. (2023). FABP5 suppresses colorectal cancer progression via mTOR-mediated autophagy by decreasing FASN expression. Int J Biol Sci, 19(10), 3115-3127.

Yin, J., Zhu, W., Feng, S., Yan, P., & Qin, S. (2024). The role of cancer-associated fibroblasts in the invasion and metastasis of colorectal cancer. Front Cell Dev Biol, 12, 1375543.

Zaramella, A., Arcidiacono, D., Nucci, D., Fabris, F., Benna, C., Pucciarelli, S., Fassan, M., Fantin, A., De Re, V., Cannizzaro, R., & Realdon, S. (2023). Resident Esophageal Microbiota Dysbiosis Correlates with Cancer Risk in Barrett's Esophagus Patients and Is Linked to Low Adherence to WCRF/AICR Lifestyle Recommendations. Nutrients, 15(13), 2885.

Zhao, L., Hou, X., Feng, Y., Zhang, Y., Shao, S., Wu, X., Zhang, J. J., & Zhang, Z. (2024). A chronic stress-induced microbiome perturbation, highly enriched in Ruminococcaceae_UCG-014, promotes colorectal cancer growth and metastasis. Int J Med Sci, 21(5), 882-895.

Zheng, Y., Yang, W., Jia, Y., Ji, J., Wu, L., Feng, J., Li, Y., Cheng, Z., Zhang, J., Li, J., Dai, W., Xu, X., Wu, J., Zhou, Y., & Guo, C. (2023). Promotion of colorectal cancer cell death by ezetimibe via mTOR signaling-dependent mitochondrial dysfunction. Front Pharmacol, 14, 1081980.

Zheng, Y. N., Lou, S. Y., Lu, J., Zheng, F. L., Tang, Y. M., Zhang, E. J., Cui, S. L., & Zhao, H. J. (2024). Selective PI3Kdelta inhibitor TYM-3-98 suppresses AKT/mTOR/SREBP1-mediated lipogenesis and promotes ferroptosis in KRAS-mutant colorectal cancer. Cell Death Dis, 15(7), 474.

Zheng, Z., Wei, Q., Wan, X., Zhong, X., Liu, L., Zeng, J., Mao, L., Han, X., Tou, F., & Rao, J. (2022). Correlation Analysis Between Trace Elements and Colorectal Cancer Metabolism by Integrated Serum Proteome and Metabolome. Front Immunol, 13, 921317.