Yan Leyfman, Co-Founder & Executive Director of MedNews Week, Executive Committee Member at Music Beats Cancer, and Medical Correspondent at OncLive, shared on LinkedIn:
“Cancer cells are remarkably adaptable, capable of changing their identity to survive, spread, and resist treatment.
In this study, the investigators identify ZFP36L2 as a key molecular switch that regulates this process in colorectal cancer.
Rather than simply controlling gene expression, ZFP36L2 helps coordinate how cancer cells respond to stress by regulating the degradation of stress-related mRNAs.
This enables tumor cells to transition back into a stem cell-like state (LGR5⁺ intestinal stem cells), a critical step for tissue regeneration and metastatic outgrowth.
Interestingly, when ZFP36L2 is lost, metastatic seeding is impaired, but tumors instead adopt alternative differentiation programs and greater lineage plasticity-features associated with poorer clinical outcomes.
These findings highlight the complexity of cancer plasticity and suggest that disrupting cell-state transitions may have very different biological consequences than previously anticipated.
This elegant study provides new mechanistic insight into how stress responses, RNA biology, and cellular plasticity intersect to drive metastasis, while identifying ZFP36L2 as a potential therapeutic target in colorectal cancer.
Congratulations to Dr. Karuna Ganesh, and the entire team at Memorial Sloan Kettering Cancer Center on this outstanding contribution to our understanding of cancer biology.”
Title: ZFP36L2 orchestrates stress-adaptive plasticity in regeneration and cancer
Authors: Qingwen Jiang, Manisha S. Raghavan, Aileen M. Rodriguez, Morgan Lallo, Cyrus L. Tam, Saskia Hartner, Britney Forsyth, Ahmed Mahmoud, Fabian Zincke, Huiyong Zhao, Andrew Moorman, Sasha Balkaran, Kathleen Luckett, Jura Pintar, Yevgeniy Romin, Eric Chan, Anthony Santella, Bernadette Mödl, Farheen Shah, Ilyes Baali, Michael G. Kharas, Elisa de Stanchina, Nil Urganci, Jinru Shia, Karuna Ganesh
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