Susanna Fletcher Greer, Chief Scientific Officer at The V Foundation, shared on LinkedIn:
“Cancer has a remarkable way of rewriting biology we thought we already understood, even one of the cell’s most basic machines.
New research from V Foundation grantee Daniel Arango, reveals how cancer cells may alter their ribosomes to drive growth, and identifies a more precise vulnerability worth pursuing.
What High School Biology Didn’t Tell Us About Cancer
I love a study that makes me reconsider something I thought I understood. Most of us learned in a high school biology class (when we weren’t dissecting frogs), that ribosomes are a cell’s tiny protein factories.
Their ‘job’ is to read genetic instructions and then to build the proteins that cells need to survive. Full stop. That was it. Memorize it and move on! So, for a long time, we all did, and the field thought of ribosomes as pretty basic machines: essential, sure, but not especially dynamic. Welp.
We were wrong: it turns out that cancer may be changing the ribosomal machinery itself.
In a new study published in Nature Communications, the V Foundation grantee Dr. Daniel Arango and colleagues at Northwestern University discovered that a protein called NAT10 helps cancer cells produce altered ribosomes that support faster growth.
NAT10 performs several ‘jobs’ in a cell, and much of the previous research has focused on its ability to chemically modify, or change, RNA. But Dr. Arango and team wanted to know which part of NAT10 actually matters most for cancer-cell proliferation.
Because, if we know how cancer cells divide, then maybe we can stop it.
The team systematically tested nearly 2,000 mutations across NAT10 to determine which parts of the protein cancer cells depend upon to divide. They then validated what they found in liver and blood cancer cells and in animal models.
The answer was surprising: the critical regions of NAT10 were not the parts that researchers have previously focused on. Instead, the team identified its RNA helicase domain, the portion that binds and interacts with RNA, as the critical driver of cell division.
Why does this matter? We weren’t talking about helicases in HS for sure.
Well, through this helicase domain, NAT10 helps cancer cells build altered ribosomes that are missing one of the chemical modifications normally found on ribosomal RNA.
These ‘hypomodified’ ribosomes seem to give cancer cells a growth advantage. When Dr. Arango disrupted key parts of the helicase domain, cancer-cell proliferation and tumor growth declined.
The reason this finding is so interesting and will be hugely impactful is because specificity matters enormously in drug development. It is not enough to know that a protein is associated with cancer.
We need to understand exactly what it is doing, which part of it is essential and what might happen if we interfere with that function. Dr. Arango has just handed the field a much more precise target to pursue.
This is preclinical work, and we still need to determine whether NAT10’s helicase activity can be targeted, and can it be done safely and effectively. But it’s critical research as it gives us a new way to think about how cancer sustains its growth, and a specific vulnerability worth investigating.
Dr. Arango’s work is supported by the V Foundation’s Stuart Scott Memorial Cancer Research Fund. This is the kind of research I am so proud that we fund.
Why? Because it’s risky. It’s fundamental to progress. Dr Arango asked a basic, but very new question about how cancer works, challenged an existing assumption, and in doing so, opened a path toward a more precise treatment.
We can all go back to school: here progress happened when we looked again at a piece of biology we thought we already understood.”
Other articles featuring Susanna Fletcher Greer on OncoDaily.