Colon cancer is a malignant tumor of the digestive tract that occurs in the colon of the human body, mostly in the age of 40-50
With the development of society, people’s living habits have gradually undergone tremendous changes under the influence of a variety of foreign cultures.
Their preference for heavy tastes, high-sugar and high-fat diets, hunger and satiety, unclean diets, and staying up late all make the incidence of colon cancer increasing.
Recently, the top academic journal "Nature" published three consecutive heavy articles that debunked the "trick" of cancer cells and provided new prevention strategies for people at high risk of colon cancer
At the same time, "Nature" also published an online News & Views titled Cancer stem cells in the gut have a bad influence on neighbouring cells, providing important insights into the dynamics of competition between cancer cells and their neighboring cells in the intestine
As we all know, stem cells are a type of cells with infinite or immortal self-renewal ability that can produce at least one type of highly differentiated progeny cells.
If cancer stem cells in the body are not completely eliminated, mutated intestinal stem cells will It will "instigate" surrounding healthy cells and inhibit the activity of surrounding healthy intestinal stem cells, allowing cancer to recur and metastasize
The adenomatous polyposis colon (APC) gene in stem cells, as a tumor suppressor gene for colorectal cancer, is the most common site of germline and somatic mutations
When this gene is mutated, it will induce the phosphorylation and degradation of β-catenin, negatively regulate the WNT pathway, and induce colon cancer
To this end, scientists have been committed to eradicating cancer stem cells
In recent years, with the advancement of technologies such as deep-targeted DNA sequencing, researchers have noticed that cancer-related mutant genes have already been latent in normal human tissues
Therefore, in order to explore the interaction between cancer-promoting mutant cells and normal neighboring cells, researchers at the Cambridge Stem Cell Institute developed a microscopy technique that uses multicolor labeling technology to track the trajectories of single mutant genes Kras and Pik3ca , Studies have found that mutated cancer stem cells can secrete specific cytokines and inhibit the activity of surrounding healthy intestinal stem cells
Of course, the research process of researchers does not stop there
Researchers from Cancer Research UK have established an in vitro cell culture system that allows single cells to develop into "small intestinal organoids" in an in vitro environment to assess the viability of stem cells
Excitingly, the experiment found the key vector of Apc mutation, "NOTUM gene".
Compared with normal cells, this gene showed higher expression in the Apc mutant cell lineage and can be used to prevent Apc mutant colorectal.
It is a cancer target and can inhibit NOTUM through genetic or drug means, thereby inhibiting the expansion of Apc mutant cells and the formation of intestinal adenomas
In order to further study the mechanism of the interaction between normal and malignant stem cells, researchers at the University of Amsterdam Medical Center in the Netherlands built mouse and human bowel cancer models mediated by Apc gene inactivation and found that APC-mediated β-catenin is one This kind of gene expression regulator that helps maintain the state of intestinal stem cells will actively inhibit the growth of neighboring cells and even induce the apoptosis of wild-type intestinal stem cells
Moreover, cancer stem cells carrying Apc mutations have a stronger competitive advantage compared to normal stem cells.
This advantage is due to the ability of Apc mutant cells to secrete WNT antagonists, which not only inhibits the activity of normal stem cells, but also promotes their differentiation
The latest research has found that lithium chloride can eliminate the inhibitory effect of WNT antagonists, providing a new strategy for the prevention of bowel cancer
So far, the focus of medical research in the field of cancer has been on the promotion of immune system-mediated defenses
However, the importance of stem cells and tissue environment to tumors is slowly being explored.
In future further research, if the WNT signaling pathway can be restarted and the function of NOTUM can be restricted in mouse models of Apc gene mutations, it is expected Inhibit the occurrence and development of tumors
All in all, these three breakthrough studies provide new ideas for future cancer treatments, which can eliminate the competitive advantage of cancer by inhibiting the differentiation of malignant tumor stem cells.
In the future, scientists are expected to develop new anti-cancer therapies based on this feature.