The Lef1 gene inhibits the development of cancer stem cells niches in order to suppress the growth of colorectal cancers

These new findings from research will help us understand how various kinds of intestinal cancers develop. They found that the Lef1 gene hinders the growth and development of colorectal cancer by limiting the development of niches in cancer stem cells.

In the most recent issue of Science Advances, cancer researchers from the iCAN Digital Precision Cancer Medicine Flagship at the University of Helsinki and HUS Helsinki University Hospital report novel research findings regarding stem cells in benign tumors of the gut where colorectal cancer develops. They show that the Lef1 gene inhibits the growth and development of cancer by restricting the development of cancer stem cells niches. The Lef1 gene is induced in tumors that are known as adenomas of the gut.

Lef1 gene blocks the creation of cancer stem cell niches

What makes this report unique is the fact that cancer stem cells are important targets for treatment of cancer. Stem cell niches in cancer aid stem cell growth in specific regions of the tumor’s microenvironment. Investigators discovered that tumor growth was dramatically increased when Lef1 gene expression was blocked.

The Lef1 gene was first discovered 30 years ago, and 20 years ago its function was associated with colorectal cancer. It was thought that Lef1 is similar to its cousin, the Tcf4 gene, by promoting cell growth in the healthy intestine as well as benign polyps and adenomas.”

Kari Alitalo (Academician, University of Helsinki), corresponding author of this study

The latest findings of the team now show the opposite. The Lef1 gene, unlike its relatives, is not expressed in healthy intestinal stem cells or crypts of. However, it is activated in the precursor cells that later develop into intestinal cancer cells.

Researchers also found that the human Lef1 gene is not activated in so-called serrated cancers of the large intestine, referring to the serrated pattern on the surface of the tumor formed by proliferating stem cell crypts.

Results may help to find new treatment targets

The new research findings help to understand the mechanisms that are responsible for different kinds of intestinal tumors. The results may also help to identify new targets for treatment. The Lef1 gene regulates the activities of the downstream genes in a hierarchical fashion. Future research could find new targets for blocking cancer stem cell genes.

Since targeted therapies for cancer stem cells are key to the treatment of cancer and other, more differentiated tumor cells have a shorter time to live without treatment. In the normal intestine most differentiated cells, such as those that produce mucus or intestinal hormones, or transport food items to the body, are able to regenerate from stem cells in accordance with an intricate genetic program within less than a week. In the meantime, “old” intestinal cells are eliminated from the feces.

This genetic program is disrupted when DNA damage activates or inactivates the cancer gene. The cells that are affected by the mutation are not able to expand further, and are therefore susceptible to mutations in the other genes that are necessary to develop and grow into malignant cancer. This is usually slow and takes years. It is therefore recommended to eliminate any pre-ceedings of intestinal cancer through the endoscopy of the intestinal, especially for elderly people.

Journal reference:

Heino, S., et al. (2021) Lef1 restricts ectopic crypt formation and tumor cell growth in intestinal adenomas. Science Advances.

Content Source:

Gemma Wilson

Gemma is a journalism graduate with keen interest in covering business news – specifically startups. She has as a keen eye for technologies and has predicted quite a few successful startups over the last couple of years.

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