A new alternative cell growth pathway could lead to better treatments for metastatic cancers

Researchers have a basic understanding of the growth of primary cancer cells, but less is known about metastasis, the deadly process by which cancers spread. A team led by Dr. Paul Krebsbach, Dean of UCLA's Faculty of Dentistry and Professor of Periodontics, discovered that the mEAK-7 gene, discovered last year, could play an important role in cancer metastasis, at least in lung cancers.

Building on this earlier genetic discovery in human cells, the team compared expression levels of mEAK-7 in normal and cancerous cells using genetic information from multiple baseline tumor cells. data as well as tissue samples from cancer patients.

"Focusing on non-small cell lung cancer, we found that mEAK-7, which is important for cell proliferation and migration, was highly expressed in non-small cell metastatic lung cancer", said Dr. Joe Nguyen, first author and postdoctoral fellow. researcher at the National Cancer Institute. "We also found that MEAK-7 is expressed in primary cancer cells but not in non-cancer cells, which shows that the protein could be a critical culprit in cancer metastasis."

The research was published in the journal iScience.

The researchers also discovered that MEAK-7, badociated with a large molecule called DNA-PKcs (which helps regulate DNA repair and control or that promotes cancer growth), has created a signaling pathway Alternative mTOR used by cancer cells for growth and proliferation. In normal cells, two well-studied pathways are controlled by a gene called mTOR, which regulates the growth, proliferation, and survival of normal cells.

"This third complex or pathway is very important for cancer stem cells, which start the process of colony formation and cell proliferation, and lead to metastasis, the leading cause of death in most cancers," said Krebsbach. "We determined that tumors and lymph nodes in patients with metastatic cancer had elevated levels of mEAK-7 protein." The development of mEAK-7 inhibitors could be beneficial for patients with Metastatic cancer with aberrant mTOR signaling badociated with elevated levels of mEAK-7. "

The researchers, who also examined these signaling molecules in cancer stem cells, determined that the new "third" mTOR complex in cancer cells was composed of mTOR, mEAK-7 and DNA-PKcs.

"Understanding the molecular interactions of metastatic cancer is crucial for determining cancer treatments at these later stages," said Jin Koo Kim, co-author and researcher of the UCLA Dentistry project. Currently, treatments for solid tumors include surgery and radiation therapy, however, many patients relapse because the target tumors develop resistance to radiation and other treatments, and this study has shown that this resistance is correlated with a higher expression of mEAK-7 in cancer cells. "