The most dangerous aspect of cancer is not the initial tumor itself, but its ability to move to other parts of the body, a process called metastasis and is responsible for most cancer-related deaths. This journey of cancer cells from origin to distant organs involves complex transformations that allow them to migrate and settle in new territory. This transformation is facilitated by the process of causing cancer cells to change their characteristics, lose their fixity and gain the ability to move and invade. Understanding this shift elucidates cancer elucidation behavior and opens the door to potentially pioneering treatments targeting these cellular chameleons.
The team led by Dr. Ana-Maria Dragoi of LSU Health Shreveport, with Madison Catalanotto, Camille Abshire, Reneau Youngblood and Min Chu of the same institution, together with Joel Markus Vaz of Georgia Technical College and Herbert’s collaboration with Levine of Northeastern University and Indian Academy of Sciences Dr. Mohit Kumar Jolly made a major breakthrough in understanding the spread of cancer. They discovered an important role for a protein called Flash in controlling the transformation process, which allows cancer cells to spread, called epithelial to interstitial transition (EMT).
This process is critical for the separation of the cancer cells from the initial tumor and moving to other body parts. The team’s findings, published in the Journal of Translation Oncology, show how the lack of flashes causes cancer cells to exhibit mixed characteristics in which non-invasive behavior has coexistence with aggressive characteristics. Dr. Ana-Maria Dragoi pointed out that “firstly, we found that the flash controls the epithelial fixation state of cancer cells. Now we know that regulation is more complex and that flash controls multiple aspects of cell transformation in cancer”, pointing out its in-cancer Key role in progress and spread. Interestingly, as cells develop, all cells temporarily increase throughout the cell cycle and play a key role in generating scaffolding proteins (histones) that DNA wraps around DNA.
By utilizing advanced RNA sequencing and computational analysis, the research team identified the unique role of Flash in inhibiting fixed cell markers and affecting genes associated with cell motility. They examined data from the Encyclopedia of Cancer Cell Lines (CCLE) to confirm the inverse relationship between flash expression and marker across cell epithelial phenotypes of different cancer types. Consistent with data from their RNA sequencing, in some cancer types, flashes are also inversely proportional to the markers of cancer cell transformation. Dr. Dragoi added: “We demonstrated the inverse relationship between flash expression and markers of invasive and cancer-fixed behaviors, but when cancer cells lack flash, they are generally less aggressive”. These confusing results suggest that Flash plays a complex dual role in regulating cell fate and is linked to previous data, suggesting that the most aggressive cancer cells have mixed characteristics.
This approach can examine in detail the role of genetic and molecular behavior that drives cancer cells, allowing science to be used by a wide audience and pave the way for innovative cancer treatment strategies. Understanding how Flash controls the cellular conversion process may lead to new treatments that will provide hope for more effective cancer treatment in the future. “These findings emphasize the importance of Flash in the ability to adapt and survive cancer, marking it as a promising goal of future therapies,” Dr. Dragoi stressed. “This study represents what we have stepped forward in our understanding of cancer biology.” An important step and a new direction for the development of targeted cancer therapies has been introduced.
Journal Reference
Madison Catalanotto, Joel Markus Vaz, Camille Abshire, Reneau Youngblood, Minchu (Min Chu), Min Chu, Herbert Levine, Mohit Kumar Jolly, ana-maria dragoi, “casp8ap2/ Dual Role Oncology of Flash, 2024. doi: https://doi.org/10.1016/j.tranon.2023.101837.
About the Author
Dr. Ana-Maria Dragoi He is an assistant professor in the Department of Physiology at LSU Health Shreveport. Her laboratory studies the intrinsic and external factors that regulate cancer metastasis in the context of cell cycle progression, as well as the intrinsic and external factors that regulate cancer metastasis in the context of oncogenic reprogramming. Dr. Dragoi is a member of the American Cancer Research Association and the American Society of Microbiology.
Dr. Mohit Kumar Jolly He is an associate professor in the Department of Bioengineering in the Indian Institute of Science. His research integrates systems biology approaches and experimental approaches to elucidate molecular drivers of cancer metastasis and cancer resistance. Dr. Jolly is the editor-in-chief of NPJ Systems Biology & Applications. He is a young scientist for the 2022 INSA Medal and a winner of the 2023 ICTP Award.
Dr. Herbert Levine He is an outstanding professor of physics and bioengineering at Northeastern University. His research focuses on epithelial to mesenchymal transition plasticity, genetic regulation of cell fate, and computational and physical modeling of the interaction between tumors and the immune system. Dr. Levine is a member of the American College of Arts and Sciences and the National Academy of Sciences and is co-director of the NSF Center for Theoretical Biophysics (CTBP) of Rice University.
