Scientists Identify Protein Combination That Can Stop Lung Cancer Growth

Scientists may have figured out a brand new way to treat lung cancer by using a protein that inhibits tumor growth.

This previously unknown molecule pathway could help researchers develop personalized lung cancer treatments, a new study in the journal Proceedings of the National Academy of Sciences (PNAS) reveals.

The researchers found that a protein called RBM10—previously known to be a tumor suppressor—can inhibit the growth of lung cancer by stopping the function of another protein called c-Myc. c-Myc drives cancer cell growth when it is overexpressed in the body.

In the study, the scientists describe how they used RBM10 to partner with two other proteins, RPL5 and RPL11, to destabilize c-Myc and prevent the proliferation of lung cancers.

"Like other types of cancers in internal organs, lung cancers take many years to develop often due to two major factors. 1) genetic alternations (gene mutations or amplifications) of cancer-related genes, such as tumor suppressor genes with p53, PTEN and RBM10 as representatives or oncogenes with RAS, EGFR, or c-Myc as representatives, caused by smoking or other air polluted substances or carcinogens, and 2) micro-environmental changes," study co-author Hua Lu, the Reynolds and Ryan Families Chair in Translational Cancer at the Tulane University School of Medicine, told Newsweek.

"If genetic alternations occur in a tumor suppressor gene, such as RBM10, this will disable its anti-cancer functions, whereas if genetical alternations, such as amplification (making more copies of oncoproteins), occur in an oncogene, this would often equip or enhance the oncogenic ability of this oncogene-encoded protein, called oncoprotein, such as c-Myc."

Proteins are made in the cell by little organelles called ribosomes, which read the code of our DNA—after being transcripted into mRNA—and translate it into proteins. Cancers can occur when the DNA being read is mutated, causing the cell to grow and reproduce uncontrollably. The c-Myc protein encourages cancer growth due to its role in the protein production process, as it allows proteins to carry on being produced despite a cancerous mutation, forming tumors.

"C-Myc is a transcriptional factor that can activate the expression of a large number of genes important for cancer cell growth, such as ribosomal proteins that are crucial for protein production needed for a cell or a cancer cell to survive or growth," Hua said.

"C-Myc also regulates immune systems by allowing cancer cells to escape from immune cells' attack. Make a long story short, c-Myc is essential for any cell growth and survival, including cancer cells. This is why cancer cells love c-Myc and desperately needs lots more of this protein for their living."

The scientists found that RBM10, with the help of RPL5 and RPL11, can destabilize c-Myc and therefore prevent it from boosting cancer growth. They also found that in lung cancers, there is often a mutant form of RBM10 that no longer suppresses c-Myc and cannot bind to RPL5 and RPL11, therefore promoting tumors rather than suppressing them.

"In this current study, we found that RBM10 can partner with RPL5 and RPL11 to downregulate c-Myc activity. Because c-Myc is essential for lung cancer cell growth, inhibition of this function would stop cancer cell growth and survival, consequently killing cancer cells," Hua said.

The researchers hope to use these findings of RBM10's functions and role in cancer suppression to develop drugs to treat lung cancer by targeting RBM10 itself.

"[There are] two ways to do so: 1) reactivate missense mutant RBM10 by converting its mutant to normal form; 2) define shorter and functional domains of RBM10 as active units against c-Myc activity, and by doing so, we could utilize the short peptide as a therapeutic agent for cancer therapy by leading to breakdown of c-Myc," Hua said.

"This approach has one advantage that is the RBM10-derived peptide is our human native protein that will not cause any immune resistance or immune reactions as a side effect."

This mechanism may also help treat other types of cancer.

"It will be useful and informative to more than 10 other types of cancers, such as liver, breast, cervical, melanoma, pancreatic, head/neck, and so on, because RBM10 is also mutated or disabled in these cancers," Hua said.

Update 11/30/23, 12:07 p.m. ET: This article was updated to include comments from Hua Lu.

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