Chinese research finds new mechanisms for chronic stress-promoting cancer development

Medical Network April 2, cancer has become one of the serious threats to human life and health, and cancer patients are often accompanied by anxiety, despair, fear and other negative emotions, which often accelerate the progress of patients' disease and affect the prognosis of patients.

Recently, a study on the relationship between chronic stress and cancer development was published in the Journal of Clinical Investigation, the authoritative journal of the international natural sciences. The study found that chronic stress can promote abnormally elevated levels of adrenaline, which promotes the dryness of breast cancer stem cells by altering the glycolytic level of breast cancer, thereby promoting the dryness of breast cancer stem cells. mechanism.

This achievement was led by the “Innovation Team” leader of the Ministry of Education of Dalian Medical University, the national young and middle-aged science and technology innovation leader, and the “Changjiang Scholar” of the Ministry of Education, Professor Liu Qiang and his research team.

Liu Qiang said that the cancer has now become a serious threat to human life and health disease, and cancer patients are usually accompanied by anxiety, despair, fear and other negative emotions, which tends to accelerate the progress of the patient's course, affect the prognosis. However, the carcinogenic effects and specific mechanisms of chronic stress caused by adverse emotions are unclear.

The research team led by Liu Qiang used a chronic stress mouse model to find that chronic stress will lead to abnormal hormone levels in mice, especially elevated levels of adrenaline, while abnormally elevated adrenaline can significantly enhance the dry characteristics of breast cancer. It can also promote the expression of the key factor lactate dehydrogenase (LDHA) in the specific effect of the Warburg effect in tumor cells to accelerate the glucose metabolism process of breast cancer cells, and provide the growth and proliferation of breast cancer cells. Energy.

Lactate dehydrogenase is the last rate-limiting enzyme in the glycolysis process, which converts pyruvate into lactic acid. Its abnormally high expression causes the accumulation of catalytic products (lactic acid), which causes the local pH of the cells to decrease. By mimicking the acidic environment of cells in vitro, the researchers found that the acidic environment created by elevated LDHA promoted the direct binding of deubiquitinating enzyme USP28 to the oncogene MYC and reduced the ubiquitination level of MYC to stabilize its protein expression.

Further studies have found that MYC can increase the expression of SLUG at the mRNA level. Using a dual-fluorescence reporter system, the researchers confirmed that MYC binds to the promoter of SLUG and increases the expression level of SLUG by promoting its transcription, thereby enhancing the dry characteristics of breast cancer. This regulatory pathway reveals the underlying mechanisms of chronic stress affecting the development of breast cancer, and validates the association between adrenaline levels and LDHA/USP28/MYC/SLUG expression in breast cancer blood samples and clinical tumor samples, and predicts poor prognosis. .

Liu Qiang said that cancer patients such as breast cancer, ovarian cancer and stomach cancer are often accompanied by bad emotions, which in turn accelerates the development of their own tumors. Then, in daily life, in addition to their own feelings, what are the objective ways to judge bad emotions? Liu Qiang said that the patient's bad mood and stress status can be comprehensively assessed through a traditional psychological assessment scale combined with clinical blood index tests (such as adrenaline levels).

In addition, in order to further find effective therapeutic drugs, Liu Qiang team used the FDA approved drug screening system to screen out the potential therapeutic drug vitamin C (Vitamin C) targeting LDHA. Through a series of experiments, Vitamin C can significantly reverse the carcinogenic effect of adrenaline on breast cancer.

This study focuses on the hot issues of chronic stress affecting the development of tumors , and clarifies that the up-regulation of adrenaline levels in chronic stress-induced breast cancer patients reconstitutes the tumor glucose metabolism pathway, thereby promoting the dry characteristics of breast cancer stem cells; Further screening out the effective therapeutic drug Vitamin C significantly reversed the tumor progression caused by chronic stress, providing a new idea for the clinical treatment of cancer patients in the future, and bringing the gospel to breast cancer patients.

The research was jointly funded by the National Natural Science Key Fund, the Guangzhou Science and Technology Planning Project, and the Dalian High-Level Talent Innovation Program.