Uncovering The Key Role of Key Genes in The Development of Colorectal Cancer

In the world of cancer, colorectal cancer (CRC) is undoubtedly a warning name. It is not only the second leading cause of cancer-related death in the world, but also a complex molecular maze. Although scientists have revealed some molecular changes associated with colorectal cancer, how these changes drive the development of cancer remains an unsolved mystery.

Recently, in a research report entitled "SOX9 suppresses colon cancer via inhibiting epithelial-mesenchymal transition and SOX2 induction" published in the international journal Journal of Clinical Investigation, scientists from the University of Michigan Medical School and other institutions found that the loss of the SOX9 gene may promote tumor progression after studying mouse models and colorectal cancer tissues, and its regulatory pathway may be expected to serve as a potential target for future treatment.

The incidence of colorectal cancer remains high worldwide, and its complexity lies in the interaction of multiple molecular mechanisms. Among them, APC gene mutation is one of the most common molecular events in colorectal cancer, and about 80% of colorectal cancer patients have inactivating mutations in the APC gene. The protein encoded by the APC gene plays a key role in cell cycle regulation and cell adhesion, and its inactivation can lead to uncontrolled cell proliferation and tumorigenesis. However, the APC gene is not fighting alone, and the SOX9 gene also plays an important role.

The SOX9 gene encodes a transcription factor that plays a key role in embryonic development and tissue homeostasis. Previous studies on the role of SOX9 in colorectal cancer have been controversial. On the one hand, studies have shown that SOX9 may promote the development of colorectal cancer, while on the other hand, some studies have suggested that the reduction or loss of SOX9 expression may be a factor that promotes tumor development. This contradiction makes the exact role of SOX9 in colorectal cancer an urgent problem to be solved. In order to further explore the role of SOX9 in colorectal cancer, researchers constructed a mouse model to inactivate both the SOX9 and APC genes. The results showed that compared with mice in which the APC gene was inactivated alone, mice in which both the SOX9 and APC genes were inactivated had more aggressive tumors. These tumors not only showed a higher degree of malignancy, but were also accompanied by the phenomenon of epithelial-mesenchymal transition (EMT). EMT is a transition in the state of a cell, which enables cells originally fixed on the surface of the intestine to acquire the ability to migrate and then invade surrounding tissues, thereby providing the possibility for tumor metastasis.

Figure 1. Mouse colon lesions with combined Apc and Sox9 inactivation had enhanced dysplastic changes and invasive features compared to lesions with Apc inactivation. (Feng Y, et al., 2025)

Subsequently, the researchers further analyzed the clinical data of nearly 400 colorectal cancer patients. The results showed that about 20% of tumor samples had low or completely missing SOX9 expression levels. The overall survival rate of these patients was significantly lower than that of patients with normal SOX9 expression levels, which further confirmed the tumor suppressor role of SOX9 in colorectal cancer. In this study, the researchers revealed the dual identity of SOX9 in colorectal cancer. On the one hand, the loss of SOX9 promotes tumor progression and invasiveness, which indicates that SOX9 may be a tumor suppressor gene in some cases. On the other hand, overexpression of SOX9 may also promote tumor development, which makes the role of SOX9 more complicated. The discovery of this dual identity not only provides new ideas for the treatment of colorectal cancer, but also opens up new directions for future cancer research. In addition, the researchers also found that the loss of SOX9 is closely related to the EMT phenomenon of tumors. EMT is one of the key steps in tumor metastasis. By inhibiting the activity of SOX9, it may be hoped to prevent the metastasis of tumor cells and improve the prognosis of patients. This discovery provides a theoretical basis for the development of therapeutic strategies targeting SOX9.

Although this study has made important progress, the researchers pointed out that the role of SOX9 in colorectal cancer is not static. Different patients may show different SOX9 action patterns due to genetic background, tumor microenvironment and other factors. Therefore, future studies need to further explore the interaction between SOX9 and APC genes, as well as the specific mechanism of action of SOX9 in different subtypes of colorectal cancer.

In addition, researchers are working to translate these findings into clinical applications. By developing targeted therapeutic drugs for SOX9, it is expected to provide more effective treatment options for colorectal cancer patients. At the same time, in-depth research on SOX9 may also help scientists better understand the molecular mechanisms of colorectal cancer, thereby providing new ideas for early diagnosis and personalized treatment of cancer. In short, this study not only reveals the complex role of SOX9 in colorectal cancer, but also provides new hope for future cancer treatment.