AMPK, a special protein that plays a double-sided role in carcinogenesis, is expected to help develop new anticancer drugs

August 22, 2019 news / Bio Valley bio on / -- the basic unit of all living things is cells, the human body contains hundreds of millions of cells, and cancer can be caused by abnormal growth and division of any one of these cells, and then form a mass or tumor Studies over the past 30 years have shown that cancer is caused by mutations in the DNA of a single cell, many of which are harmless, but can be induced if they affect the DNA that provides instructions to make the proteins needed for cell growth and division Photo source: according to the traditional view of en.wikipedia.org, if the "good cop" protein is turned off and the "bad cop" protein is turned on, these changes will cause cancer The "good cop" protein can act as tumor suppressor to inhibit cell growth and division, but the latest research results show that this simple protein can inhibit tumor growth and division The classification of inhibitors and promoters may be problematic in AMPK, a special protein first defined by researchers at Dundee University in the 1980s If AMPK plays the role of "good cop" or "bad cop", it will turn on the ability to inhibit tumor, so as to help effectively inhibit the occurrence of cancer, at the same time, it will turn off the ability to promote tumor, and help researchers effectively treat diseases AMPK and its key role in cancer AMPK, adenosine monophosphate activated protein kinase, is a special protein that can modify other proteins It is activated by the decrease of cell energy level, for example, when nutrients or oxygen are insufficient due to the lack of blood supply Once activated, AMPK will activate its activity in the cell and restore the energy supply, while inhibiting cell growth and division This growth inhibitory factor suggests that AMPK may play the role of tumor suppressor; in fact, after the study in mice, researchers found that the absence of AMPK in developing B cells or T cells will accelerate the occurrence of B cells or T cell lymphoma In other studies in mice, the researchers found that if T-cell lymphoma occurs, the AMPK gene will be eliminated, and that AMPK actually plays a role as a tumor promoter AMPK usually plays the role of tumor suppressor, but despite its best efforts, the tumor will still appear, and then it will become a tumor promoter, which may be because AMPK can protect the tumor Cells resist pressure from rapid cell growth, division, and inadequate blood supply, all of which contribute to the survival of abnormal cells rather than death Enlightenment for human studies although these studies are carried out in animal bodies, the study of human cancer can be analyzed by comparing the DNA sequences of tumor tissues and surrounding normal tissues Some genes encoding AMPK components may undergo mutations in cancer, which may damage their functions; others will amplify this effect, which reveals the tumor So AMPK seems to play the role of "good cop" and "bad cop" in human cancer Photo source: en.wikipedia.org this study is of great significance In order to analyze the function of AMPK's "good police" role (tumor suppressor), drugs that enable its expression may be able to treat high-risk cancer patients What's more, the drug (metformin) already exists and is used to treat type 2 diabetes The researchers found that metformin may not be able to effectively protect mice against T-cell lymphoma, because drugs cannot enter the developing T cells, while another ancient diabetes drug phenformin can enter the cells to protect the body against lymphangioma Although phenformin is no longer used in the treatment of diabetes due to its side effects, the risk of using it in cancer prevention is also acceptable Instead, to dig deeper into the role of AMPK's "bad cop" (cancer Drugs that inhibit the function of promoters may enhance the effectiveness of therapies, such as chemotherapy and radiotherapy Interestingly, cancer is usually caused by DNA mutations Chemotherapy and radiotherapy can play a role by promoting DNA damage of cancer cells The reason why they are effective is that rapidly dividing cells, such as cancer cells, are often more effective than normal cells It is easier to be killed by DNA damage The results of this study show that AMPK can be activated by drugs in chemotherapy, so as to help cancer cells develop tolerance to treatment; inhibition of AMPK function can enhance the effectiveness of current chemotherapy or radiotherapy, although these drugs do not exist at present, but later researchers will develop corresponding drugs through more in-depth research Reference materials: [1] meditation and cancer [2] Diana vara ciruelos, Fiona M Russell, D Graham Hardie The strategy case of AMPK and cancer: Dr Jekyll or Mr Hyde? Open Biology 10 July 2019， doi：10.1098/rsob.190099 【3】 The LKB1-AMPK signalling cascade 【4】Grahame Hardie D AMP-activated protein kinase： a key regulator of energy balance with many roles in human disease J Intern Med 2014 Dec；276(6)：543-59 doi： 10.1111/joim.12268 Epub 2014 May 27 【5】 AMPK Is a Negative Regulator of the Warburg Effect and Suppresses Tumor Growth In Vivo 【6】 Phenformin， But Not Metformin， Delays Development of T Cell Acute Lymphoblastic Leukemia/Lymphoma via Cell-Autonomous AMPK Activation 【7】 AMPK Is Essential to Balance Glycolysis and Mitochondrial Metabolism to Control T-ALL Cell Stress and Survival 【8】 Metformin 【9】Diana Vara-Ciruelos， Madhumita Dandapani， Alexander Gray， et al Genotoxic Damage Activates the AMPK-α1 Isoform in the Nucleus via Ca2+/CaMKK2 Signaling to Enhance Tumor Cell Survival ， Molecular Cancer Research ，February 2018 doi：10.1158/1541-7786.MCR-17-0323 【10】 Cancer's 'good cop/bad cop' protein could help develop more effective drugs by Grahame Hardie， The Conversation