Defining Collagen-Epigenome Interactions to Reveal Melanoma Vulnerabilities

Why This Research Matters
Melanoma is an aggressive form of skin cancer that can spread to other parts of the body and become difficult to treat. While scientists have learned a great deal about the genetic mutations that drive melanoma, it is increasingly clear that cancer cells are also strongly influenced by their surrounding environment. One important part of this environment is the extracellular matrix, a network of structural proteins such as collagen that surrounds and supports cells in tissues. Changes in collagen structure and density can affect how tumor cells grow, survive, and respond to treatment. However, scientists still do not fully understand how signals from the tumor environment interact with processes inside cancer cells to promote melanoma progression.

What We Are Studying
Our research focuses on a gene called TET2, which helps control how genes are turned on and off by modifying chemical marks on DNA. Reduced activity of TET2 is commonly seen in aggressive melanomas and has been linked to changes in how tumor cells produce and use energy.

How the Study Works
Our preliminary studies suggest that the density of collagen surrounding tumor cells can influence melanoma cell behavior depending on whether TET2 activity is high or low. In particular, melanoma cells with reduced TET2 activity appear to become more metabolically active and aggressive when growing in environments with lower collagen density. The goal of this project is to understand how collagen density and TET2 activity work together to influence melanoma cell behavior and to determine whether this interaction creates weaknesses that can be targeted with new therapies. We will grow melanoma cells in laboratory models that mimic different collagen environments and use modern genomic and molecular techniques to study how gene activity and cellular metabolism change under these conditions. We will also analyze large public cancer datasets to identify drugs that may specifically target melanoma cells in this state and test promising candidates in laboratory models and mouse studies.

Expected Impact
This research will provide new insight into how melanoma cells and their surrounding environment work together to drive cancer growth. By identifying weaknesses created by these interactions, this work may reveal new strategies for treating aggressive melanoma and improving outcomes for patients.