Colon cancer remains a significant global concern about health, ranking third place among the most diagnosed cancers and cancer -related death directives worldwide. A critical factor that makes the treatment of colon cancer is the presence of cancer stem cells. Although usually present in small populations, these powerful cells lead to tumor growth, resist standardized treatments and often contribute to recurrence. They do this through their “sterling”, a set of properties that allow these cells to self -read and differentiate into other cell types. Thus, understanding how the molecular stem can be tested is essential for the development of effective therapies for colon cancer.
In the last two decades, researchers have identified several basic molecules involved both in colon development and in the development of colon cancer. Among them are CDX1 and CDX2, two Homeobox transcription factors that help create and maintain the identity of intestinal epithelial cells. Another example is beta-kathenine protein, an established colon cancer driver, whose malfunction can lead to uncontrolled cell growth. While previous studies have shown that CDX1 and CDX2 inhibit tumor growth, accurate mechanisms with which they offset beta-catein and the suppression of the executive remain largely unknown.
Now, a recent study led by Professor Koji Aoki from the Department of Pharmacology, Medical School at the University of Fukui, Japan, along with Dr. Akari Nitta and Dr. Ayumi igarashi from the same university, provides new ideas. By sharing the motivation behind their study, Professor Aoki states, “We want to understand the transcription mechanisms that form the basis of the progression of colon cancer, as well as those who regulate the differentiation and strain on colon cancer.”
Their document, published in volume 16 of the magazine Cell death and illness On May 21, 2025, he reveals that CDX1 and CDX2 interfere with beta-catein and affect the gene expression pathways that maintain strains in colon cancer cells.
Researchers used genetically modified mice models, human cell lines of colon cancer and organic crops to analyze how to delete or over -express CDX1/2 tumor behavior. They found that complete loss of CDX1 or the combined loss of CDX1 and CDX2 increased the aggression of tumors in mice. These tumors showed a higher expression of LGR5 and Cd44-Two genes strongly associated with cancer and were more invasive. When the CDX1 or CDX2 is artificially re -introduced to cancer cells, the expression of these strains -related genes has been severely reduced, indicating a repressive role of CDX1/2.
To understand the underlying molecular mechanisms, the group fell into the thinnest details of how CDX1/2 affects gene expression. Observed that CDX1/2 is bound to a particular area downstream of the starting point of LGR5 Gene, an area that also aims at beta-catein. Paradoxically, although CDX1/2 promoted an open chromatin structure usually associated with the expression of the active gene, they still significantly reduced the presence of basic transcription components, namely RNA polymerase II (Pol II), factor in DRB (DSIF) LGR5Original location. These proteins are essential for the transcript of DNA and regulate it.
Through further experimentation and analyzes, the researchers found that CDX1/2 intervenes directly into the ability of beta-catein to assemble the active form of Pol II clashes, which include DSIF and PAF1. This repression occurred because CDX1/2 prevented immediate interaction between β-katenin and these transcription factors due to their functional uniforms. Therefore, CDX1/2 effectively cut off the supply chain required for LGR5 Expression and promotion of the cancer strain.
According to Professor Aoki, identifying the roles of DSIF and PAF1 in the context of colon cancer was one of the main findings of the study. “Our results indicate that DSIFs and PAF1 complexes act as transcriptional platforms that incorporate and channel both delayed and oncogenic signals in the expression of genes controlling colon cancer strains“He explains, this puts DSIF and PAF1 complexes as central players in the pathophysiology of colon cancer, marking them as potential therapeutic goals of future drugs.
The targeting of genes and proteins that regulate fastening can become a cornerstone for new cancer treatments, although more studies will be needed to understand and utilize these complex cell processes. “Further investigation of stem -related transcription mechanisms will help develop medicines for effective treatment of colon cancer“assumes Professor Aoki.
Source:
Magazine report:
Aoki, K., et al. (2025). CDX1 and CDX2 suppress colorectal cancer, inhibiting the formation of the Pol II-DIF-PAF1C complex that facilitated beta-captainin. Cell death and illness. Doi.org/10.1038/S41419-025-07737-3.
