MEDICINE AND HEALTH

Chinese scholars have discovered the regulatory mechanism established by heterogeneity in the early stage of colorectal cancer


On June 20, the research group of Pengcheng Bu of the Institute of Biophysics of the Chinese Academy of Sciences published new research results in the international academic journal EMBO Reports, reporting the regulatory mechanism established by heterogeneity in the early stage of colorectal cancer.

Tumor heterogeneity is one of the characteristics of malignant tumors and is a barrier to effective treatment. As a malignant tumor with high heterogeneity, colorectal cancer ranks third among all cancers in incidence and third in mortality. A large number of studies have shown that colorectal cancer is caused by abnormal proliferation and differentiation of cells after the normal stem cells at the bottom of the crypt are transformed into cancer stem cells after mutation accumulation. However, how intratumoral heterogeneity is established in the early stages of tumor progression is largely unknown.

In this study, the researchers confirmed that asymmetric division of colorectal cancer cancer stem cells is critical for the establishment of early intratumoral heterogeneity based on single-cell RNA-seq and functional validation. The results showed that xenografts derived from colorectal cancer cancer stem cells contained seven cell subtypes, which were dynamically altered during colorectal cancer xenograft progression. Moreover, the study found that 3 of the cell subsets were produced by asymmetric division of colorectal cancer cancer stem cells, which were functionally distinct and appeared in the early stages of xenografts. In addition, the team identified a drug-resistant subpopulation and an invasion subpopulation and explored the regulatory factors that control the production of these subpopulations. Further studies have found that targeted regulators can influence the composition of cell subtypes and colorectal cancer progression.

This study shows that asymmetric division of colorectal cancer cancer stem cells contributes to the establishment of early intratumoral heterogeneity. Therefore, asymmetric division targeting cancer stem cells can change the composition of intratumoral heterogeneity and facilitate colorectal cancer treatment.

Chao Shanshan, Zhang Fei, and assistant researcher Yan Huowen, Ph.D. students at the Institute of Biophysics, Chinese Academy of Sciences, are co-first authors of the paper. Professor Bu Pengcheng of the Institute of Biophysics and Professor Du Junfeng of the Seventh Medical Center of the General Hospital of the People’s Liberation Army of Chinese People’s Republic of China are co-corresponding authors of the paper. This research was supported by the National Key Research and Development Program of the Ministry of Science and Technology, the Strategic Leading Science and Technology Special Project of the Chinese Academy of Sciences, and the National Natural Science Foundation of China. (Source: Meng Lingxiao, China Science News)

Related paper information:https://doi.org/10.15252/embr.202256416



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