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A4025
October 22, 2019
10/22/2019 7:45:00 AM - 10/22/2019 9:45:00 AM
Room WA2 - Area C
Fasting Suppresses Aerobic Glycolysis and Proliferation of Colorectal Cancer via FDFT1-mediated AKT/MTOR/HIF1A Pathway
Meilin Weng, M.D., Wankun Chen, M.D., Changhong Miao, M.D.
Fudan University Shanghai Cancer Center, Shanghai, China
Disclosures: M. Weng: None.W. Chen: None.C. Miao: None.
Patients with colorectal cancer still have poor prognoses, though much efforts have been made to understand the molecular biological aspects of this disease. Accumulated evidences suggest that fasting has extensive anti-tumor effects in a variety of cancers, including colorectal cancer. In addition, fasting can resist the side effects of chemotherapy, combat a variety of surgical stress, reduce organ damage, and improve cognitive function. However, whether these results will affect the management of perioperative diet, there is no consensus. Meanwhile, the mechanism by which fasting inhibits colorectal cancer remains poorly understood. Here, we sought to elucidate the function of fasting on colorectal cancer glucose metabolism and malignancy. We found that fasting up-regulates the expression of a cholesterogenic gene, Farnesyl-Diphosphate Farnesyltransferase 1 (Fdft1) during inhibiting colorectal cancer aerobic glycolysis and proliferation by proteomics and GEO analysis. Furthermore, the down-regulation of Fdft1 is correlated with malignant progression and poor prognosis in colorectal cancer. Thus, Fdft1 acted as a critical tumor suppresser in colorectal cancer. Then, we observed that Fdft1 is an important downstream target of fasting in inhibiting colorectal cancer aerobic glycolysis and proliferation. Mechanistically, Fdft1 exerts its tumor inhibitory function by negatively regulating AKT/mTOR/HIF1α signaling. We conclude that fasting serves as a negative regulator in glucose metabolism and proliferation via Fdft1/AKT-mTOR-HIF1α axis in colorectal cancer. These results indicate a novel function of Fdft1 in colorectal cancer glucose metabolism, and suggest that Fdft1 can be a potential marker and therapeutic target for colorectal cancer. Our results also shed light on potential therapeutic implications (fasting, Fdft1 and AKT/mTOR/HIF1a signaling) for colorectal cancer during perioperative management. Our research can provide more theoretical basis for perioperative diet management. We believe that perioperative fasting is likely to be a potential preventive means to protect organs and tissues, resist stress, reduce perioperative complications, and improve the prognosis of cancer patients.Our research can provide more theoretical basis for perioperative diet management. We believe that perioperative fasting is likely to be a potential preventive means to protect organs and tissues, resist stress, reduce perioperative complications, and improve the prognosis of cancer patients.$$graphic_{FD08E964-5C7B-464E-A413-F6A7378C8B9A}$$
Figure 1

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