Research Summary: Our study shows that the IL-9–HIF-1α–Cofilin-1 pathway drives malignant T-cell spread in advanced CTCL. Blocking it with drugs like echinomycin offers a potential strategy to control progression.
Author interview
Ditipriya Mukherjee is a doctoral candidate at IIT Bombay under Professor Rahul Purwar. She studies cytokine-driven tumor progression in hematological malignancies, investigating novel pathways that promote immune evasion and metastatic behavior.
LinkedIn: www.linkedin.com/in/ditipriya-mukherjee-711721152
Lab: Prof. Rahul Purwar, Indian Institute of Technology Bombay
What was the core problem you aimed to solve with this research?
Cutaneous T-cell lymphoma (CTCL) is a rare cancer that begins in the skin and gradually spreads to vital organs. Once it disseminates, treatment becomes very difficult as standard therapies like topical ointments no longer work and alternatives can cause side effects such as anemia and tachycardia. Our goal was to uncover the signaling network that drives malignant T-cell migration and lesion spread, so that we can target this pathway specifically to slow disease progression with fewer side effects.
How did you go about solving this problem?
We combined patient samples, cancer cell lines, and advanced lab techniques to trace how IL-9 drives malignant T-cell migration. We also performed innovative time-lapse experiments and generated videos to track single-cell movement under IL-9 or drug-treated conditions. Along with proteomics and gene-silencing approaches, this helped us identify the IL-9–HIF-1α–Cofilin-1 pathway as the key driver. Finally, we tested whether blocking this pathway with the drug echinomycin could halt cancer cell spread — and it did.
How would you explain your research outcomes (Key findings) to the non-scientific community?
HIF-1α, a transcription factor, is upregulated when IL-9 binds to its receptor, IL-9R. A transcription factor’s role is to regulate gene expression in the nucleus; in this case, HIF-1α activates the gene CFL-1, leading to higher production of the protein cofilin-1 (CFL-1). Cofilin-1 is responsible for regulating actin polymerization and depolymerization — a dynamic process called tread-milling that controls the cytoskeleton. When CFL-1 levels rise, actin turnover accelerates, ultimately increasing cell motility.
Think of this process like a game of passing the parcel. IL-9 binding to its receptor is the signal to start the game. The ‘parcel’ being passed is the message to move. HIF-1α takes the first handoff and passes it to cofilin-1. Finally, cofilin-1 delivers the parcel to the cell’s edge, where it pushes the cell forward, making it more mobile. This chain of signals is what enables cancer cells to spread.
What are the potential implications of your findings for the field and society?
Our findings highlight a new way in which cancer cells spread in cutaneous T-cell lymphoma. By uncovering the IL-9–HIF-1α–Cofilin-1 pathway, we not only provide researchers with a fresh therapeutic target but also show that existing drugs like echinomycin could be repurposed to block this spread. For patients, this means hope for more effective treatments that control disease progression with fewer side effects, ultimately improving quality of life and survival. My supervisor, Prof. Rahul Purwar, often emphasizes that research should be meaningful—it doesn’t have to be something monumental or out of the world, but it should create a real impact on society. Even if our work benefits just one patient, that contribution is valuable, and I believe this philosophy underpins the broader implications of our findings.
What was the exciting moment during your research?
There were many exciting moments during this research. A thrilling moment was when we finally got clear time-lapse videos from our 3D migration assays, showing dramatic differences in how IL-9–treated versus untreated cells moved.
Working directly with patient samples and preparing tissue sections was also a valuable and memorable learning experience.
During the review process, a reviewer suggested testing whether overexpressing the IL-9 receptor would amplify the pathway. At first, I was skeptical, but when we did the experiment, the results were striking — cells with extra IL-9R showed a much stronger HIF-1α response than normal malignant cells. That actually confirmed just how robust this signaling axis is.
Finally, the highlight was receiving the email that our paper had not only been accepted but also selected for the journal’s cover — especially meaningful since I’ve always been passionate about the beauty of multi-colored stained images.
Paper reference: Mukherjee D, Marathe S, Attrish D, Sawant V, Dhamija B, Kumar S, Wad S, Basu M, Sharma N, Jain H, Barthel SR, Purwar R. IL-9 Promotes Migratory Dissemination of Malignant T Cells by Activating the HIF-1α-Cofilin-1 Axis in Cutaneous T-cell Lymphoma. Mol Cancer Res. 2025 Sep 4;23(9):807-821. doi: 10.1158/1541-7786.MCR-24-1020.
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