Researchers find that recently identified gene may be linked to cancer metastasis

UCLA researchers have found that a gene discovered in 2018 may be linked to lung cancer growth.

UCLA and University of Michigan researchers were the first to identify the gene mEAK-7 and its role in cell growth in 2018. Building upon this research, the intercampus team has now discovered that mEAK-7 gene expression is strongly correlated with certain types of metastatic lung cancers, especially those resistant to both chemotherapy and radiotherapy.

The resultant study on the research was published in iScience, a Cell Press journal. Last year, Nguyen said his research team, led by UCLA’s current dean of the School of Dentistry, Paul Krebsbach, was the first to determine the gene’s biological function.

Joe Nguyen, the study’s first author and postdoctoral fellow at the National Cancer Institute, began research into this gene as a University of Michigan student after learning about gene EAK-7, which played a role in determining the lifespan of worms. Once Nguyen and his team found the human counterpart of this gene, they named it mammalian EAK-7, or mEAK-7, for short.

“When I worked in Dr. Kresbach’s lab, I was interested in studying this new gene’s function in the context of stem cell biology,” Nguyen said. “As we dug further, we found that it actually plays a more important role in tumor biology by regulating mTOR signaling.”

Co-author Jin Koo Kim, a project scientist at UCLA’s School of Dentistry, said mTOR signaling refers to a metabolic pathway all cells use to make proteins and grow. However, when the mEAK-7 gene is expressed, Kim said it can inhibit the typical mTOR pathway and cause unregulated growth, proliferation and eventually metastasis in cancers. Metastasis occurs when cells from a tumor enter the bloodstream, creating other cancerous colonies throughout the body.

Although the team’s research focused on lung cancer, Kim said high levels of mEAK-7 expression is present in multiple cancers such as breast and colorectal cancers.

“(The mTOR pathway) is super necessary for cell growth, proliferation and a lot of basic cell functions,” said Fatima Haidar, a study co-author. “But when you begin to mess with those functions, you begin to create a disease state, and in this case it’s cancer.”

Kim said the correlation between abnormal mTOR signaling and cancer growth had been established decades ago, but this knowledge was difficult to turn into effective therapies. Since all cells use mTOR signaling, it is extremely difficult to develop a drug that targets mTOR signaling in cancer cells without also harming a patient’s healthy cells, Kim said.

Haidar said their research can sidestep this issue by leading to the development of drugs that target the mEAK-7 protein instead of the mTOR pathway.

Once the research is further developed, Haidar said it could be applied to multiple types of cancer, not just lung cancer. Many cancers demonstrate high levels of mEAK-7 expression, but each cancer has a distinct mutation in the gene. Theoretically, physicians could test cells for mEAK-7 expression to determine whether a patient’s cancer is likely to metastasize and the severity of the prognosis.

“(The) mEAK-7 gene can potentially function as a biomarker for patients with metastatic cancers,” Haidar said. “So learning how to modulate mEAK-7 protein levels in a cell could be extremely beneficial for metastatic lung cancers – especially those that we find are either resistant to chemotherapies or radiotherapies. That’s the direction this is taking, towards more targeted drug delivery.”