Home Medizin Studie zeigt unterschiedliche molekulare Merkmale von proximalem und distalem Dickdarmkrebs

Studie zeigt unterschiedliche molekulare Merkmale von proximalem und distalem Dickdarmkrebs

von NFI Redaktion

Researchers at the Johns Hopkins Kimmel Cancer Center have discovered that the right and left parts of the colon have different molecular characteristics in cancer. New findings from studies in mice show that these regions also have distinct transcription programs or cellular processes that regulate the development of normal and cancerous cells.

The transcription factor CDX2, which plays a crucial role in the development and function of the digestive system, is identified as a key mediator of these differences in stem cells of the proximal (right) colon, according to the study published online on February 15th in Nature Communications. CDX2 was found to play different roles in regulating stem cell differentiation in the proximal and distal (left) colon. This difference in stem cell regulation could help explain the various features of colon cancer that occur in these two regions of the colon.

Mutations in genes like BRAF and KRAS can be found in different regions of the colon affected by cancer, leading to distinct characteristics. The study highlights the importance of understanding these molecular differences and their impact on cancer development and treatment.

The researchers derived organoids from the proximal and distal colon of two-month-old mice and introduced the oncogenic BRAF gene. Organoids are clusters of cells cultured in the lab to mimic the structure and function of specific organs, like the colon. The study revealed that CDX2 plays a crucial role in regulating stem cells and differentiated cell states, particularly in epithelial cells lining the proximal colon.

„The loss of CDX2 function immediately changes the state of the cells to promote tumor formation in the proximal colon, while this is not the case in the distal colon.“


Lijing Yang, MD, Lead Author, Oncologist at Zhongnan Hospital, Wuhan University, China

These findings have implications for developing new therapies for colon cancer, particularly in addressing resistance to existing treatments targeting genes like BRAF and KRAS. The study emphasizes the importance of understanding the underlying mechanisms that influence the initiation and progression of colon cancer in different regions of the colon.

The study was supported by grants from the National Cancer Institute, the National Institute of Environmental Health Sciences, and the Evelyn Grollman Glick Scholar Award.

Source:

Journal Reference:

Yang, L., et al. (2024). Tissue-specific transcription programs promote tumor dependencies in colon cancer. Nature Communications. doi.org/10.1038/s41467-024-45605-4.

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