May 18, 2024

Loss of RBFOX2 Protein Linked to Increased Pancreatic Cancer Metastasis

Pancreatic cancer is known for its poor prognosis and high mortality rates. A recent study published in Nature Communications sheds light on the molecular mechanisms that contribute to the progression and metastasis of pancreatic cancer.

Researchers from Moffitt Cancer Center, in collaboration with various institutions, have identified the role of a protein called RBFOX2 in the development and spread of pancreatic cancer. RBFOX2 is involved in the process of RNA splicing, which is crucial for the synthesis of proteins.

The study found that the levels of RBFOX2 protein were lower in pancreatic cancer cells that had metastasized to other parts of the body. This suggests that RBFOX2 may function as a tumor suppressor, inhibiting the spread of cancer. The researchers confirmed this hypothesis by showing that the loss of RBFOX2 in pancreatic cell lines and mouse models increased cell migration, invasion, tumor growth, and metastasis.

Further experiments revealed that RBFOX2 regulates the splicing of RNA molecules that code for proteins involved in cytoskeletal remodeling. Specifically, it was found that RBFOX2 controls the splicing of RNA coding for the protein ABI1. In the absence of RBFOX2, ABI1 is redistributed to the cell periphery, affecting the cytoskeleton and promoting cell migration.

These findings highlight the importance of alternative RNA splicing in pancreatic cancer progression and suggest the need for further research to fully understand the mechanisms of RBFOX2 splicing activity.

According to Karen Mann, Ph.D., from Moffitt Cancer Center, while few splicing regulators with prognostic implications have been identified in pancreatic cancer, the occurrence of conserved splicing events across different types of cancer suggests that alternative splicing plays a crucial role in cancer progression.

Pancreatic cancer is known for its aggressive nature and poor treatment outcomes. The disease is often diagnosed at an advanced stage, when it has already spread to other parts of the body. Understanding the molecular mechanisms that drive metastasis is essential for developing more effective treatments and improving patient outcomes.

The study’s findings on RBFOX2 provide valuable insights into the role of alternative RNA splicing in pancreatic cancer. By identifying RBFOX2 as a potential tumor suppressor and demonstrating its impact on cytoskeletal remodeling, the researchers have uncovered a promising target for future therapies.

Further research is needed to fully unravel the mechanisms behind RBFOX2 splicing activity and its implications for pancreatic cancer progression. By gaining a deeper understanding of these mechanisms, researchers can identify new therapeutic targets and develop strategies to effectively treat metastatic pancreatic cancer.

Overall, this study contributes to the growing body of knowledge on pancreatic cancer metastasis and highlights the potential of targeting alternative RNA splicing as a therapeutic approach. With further research and development, it is hoped that these findings will lead to improved treatment options for pancreatic cancer patients.

1. Source: Coherent Market Insights, Public sources, Desk research
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