Cell: Dietary supplement creatine promotes tumor metastasis

Cell: Dietary supplement creatine promotes tumor metastasis. Colorectal cancer is the third largest cancer in the world, with high morbidity and mortality.

Colorectal cancer

It is the third largest cancer in the world, with high morbidity and mortality, and easy to metastasize. Among them, the liver is the main metastatic organ of colorectal cancer, and liver metastasis is the main cause of death from colorectal cancer. More and more studies have shown that non-genetic factors such as abnormal cell metabolism play an important role in tumor metastasis. Therefore, the metabolic characteristics and regulatory mechanisms of bowel cancer cells will enhance our understanding and understanding of the occurrence and metastasis of bowel cancer. Intervention ability.

Creatine

It is a nitrogen-containing organic acid that naturally exists in mammals. Its classic function is to catalyze the production of creatine phosphate through creatine kinase, participate in ATP metabolism, and act as an energy buffer system to supply energy for high-energy-consuming tissues such as muscles and brains. As one of the most popular nutritional supplements, creatine is widely used by athletes and fitness enthusiasts. Creatine supplementation has been proven to have a certain therapeutic effect in clinical trials of diseases such as congenital synthetic defects, neurodegenerative diseases, and muscle atrophy. In cancer research, subcutaneous tumor-bearing mouse models show that creatine can inhibit the growth of a variety of solid tumors, so creatine has long been considered a potential tumor-inhibiting supplement.

April 2, 2021, the research group of Bu Pengcheng, the Institute of Biophysics, Chinese Academy of Sciences, the research group of Chen Gang, the Seventh Medical Center of the Chinese People’s Liberation Army General Hospital, and the Dalian Institute of Chemical Physics, Chinese Academy of Sciences
In collaboration with Park Hailong’s research group, he published an online title of “Creatine promotes cancer metastasis through activation of Smad2/3” in Cell Metabolism.
Research papers.

The paper revealed that creatine activates the Smad2/3 signaling pathway through monopolar spindle kinase (MPS1) to promote tumor metastasis.

The study found that creatine supplementation has opposite effects on healthy people and cancer patients. Creatine can increase muscle mass and exercise capacity in healthy people, but it can promote tumor metastasis in cancer patients. In addition, the study also proposed that targeting creatine synthase GATM, creatine transporter SLC6A8 and MPS1 may become potential targets for inhibiting tumor metastasis, especially for TGF-β receptor mutant colon cancer metastasis may be more effective.

Researchers found the adverse effects of creatine supplementation through orthotopic mouse models, that is, creatine can promote the metastasis of colorectal cancer and breast cancer, and shorten the survival time of tumor-bearing mice. The rate-limiting enzyme for creatine synthesis, Glycine amidinotransferase (GATM), It is up-regulated in liver metastasis. GATM-mediated creatine synthesis can also promote tumor metastasis, and inhibition of GATM expression or enzyme activity can significantly inhibit the metastasis of colon cancer and prolong the survival time of tumor-bearing mice.

In the mechanism study, researchers found that creatine can up-regulate the expression of Slug/Snail by activating Smad2/3, and promote tumor cell infiltration and metastasis. Interestingly, the activation of Smad2/3 by creatine does not depend on the TGF-beta receptor, but on MPS1. It was further found that targeting MPS1 can significantly inhibit Smad2/3 phosphorylation, tumor metastasis, and prolong the survival time of mice.

Creatine plays different functions in healthy people and colorectal cancer patients

The study found that creatine supplementation has opposite effects on healthy people and cancer patients.
Creatine can increase muscle mass and exercise capacity in healthy people, but it can promote tumor metastasis in cancer patients. In addition, the study also proposed that targeting creatine synthase GATM, creatine transporter SLC6A8 and MPS1 may become potential targets for inhibiting tumor metastasis, especially for TGF-β receptor mutant colon cancer metastasis may be more effective.

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