Susanna Fletcher Greer: Understanding cellular communication in colorectal adenocarcinoma

Susanna Fletcher Greer, Chief Scientific Officer at the V Foundation, shared a post on LinkedIn:

“This week’s Cool Cancer Find was fun to write for LinkedIn as it focuses on communication, albeit on the cellular level.

For starters, your body has a communication network that allows cells to send out an alarm when they detect danger. Cool right?! Thanks to groundbreaking research from Dr. Jianjun Wu’s team at Cleveland Clinic, funded in part by the V Foundation, we now understand more about how this system works, and how it could transform how we treat cancer.

At the heart of this discovery is the cellular messenger system called the OAS-RNase L pathway. This pathway is part of our body’s first line of defense against viral infections. When a virus enters a cell, it triggers the production of a molecule called 2-5A. This molecule in turn activates an enzyme, RNase L, which then destroys viral genetic material and helps alert the immune system to fight the infection.

We’ve known about this communication pathway for years, but until now, we thought this defense mechanism only worked inside individual cells. What Dr. Wu’s research reveals is a surprising twist: cells can actually send the 2-5A signal to their neighbors. By communicating the alarm to surrounding cells, the immune system can start a faster, and coordinated response.

So why is this discovery important for cancer patients? Well, some cancers like the once studied here (colorectal adenocarcinoma), can produce high levels of OAS and 2-5A. Dr. Wu and team showed in this study that tumors can release 2-5A, which activates RNase L, but not within the cancer cells themselves, rather in nearby healthy immune cells. This in turn kickstarts the anti-tumor immune response we’ve talked about in previous weeks, helping the body fight back against cancer.

Cool, right?!

Ok, I don’t always go deep into the science in my shares, but I want to share one final step here (communication often involves multiple team players, after all): another key player in this process is a protein called ABCC10, which helps move 2-5A from the tumor to surrounding cells. This is the most important finding from this study to me, because when ABCC10 is missing, tumors lose their ability to trigger/communicate/start this immune response, giving cancer an advantage.

Bottom line: understanding how to harness or maybe enhance this process can open new doors for developing cancer therapies that work by boosting the body’s natural defenses.

This discovery has profound implications. Through understanding how cells communicate immune signals, Dr. Wu and others can explore new ways to design cancer treatments that amplify these natural cellular defense mechanisms. For example, therapies that increase 2-5A production or enhance its transfer could improve how the immune system targets cancer.

Breakthroughs like these of course don’t happen in isolation. They require vision, LOTS of time, energy, effort, dedication, and the resources to pursue bold ideas. By funding innovative research like Dr. Wu’s, the V Foundation is accelerating discoveries that could lead to new, life-saving treatments. Go team Wu!

Find the Wu lab at Jianjun Wu Lab | Lerner Research Institute and read this awesome study at OAS cross-activates RNase L intercellularly through cell-to-cell transfer of 2-5A to spread innate immunity: Immunity.“