Key factor helps drive metastases in aggressive cancers.
Scientists may have pinpointed why pancreatic cancer becomes aggressive so rapidly.
Pancreatic cancer can be difficult to diagnose because in its early stages it produces little to no symptoms. Often, patients will not receive a diagnosis until the disease is in its later stages, has begun to metastasize, and surgery is no longer an option. The 1-year survival rate of patients with pancreatic cancer who do not have surgery is 29%, and the 5-year survival rate is 7%, according to Cancer.net.
Experts have considered partial activation of the epithelial-to-mesenchymal transition program (partial EMT) to be a major driver of tumor progression, but the role of EMT in promoting metastasis was recently challenged, particularly in the effects of the Snail and Twist EMT transcription factors (EMT-TFs)
In a new study published in Nature Cell Biology, investigators discovered why pancreatic cancer and other malignant types of tumors can disseminate so quickly.
The investigators found that this aggressive type of tumor activates the factor Zeb1, which controls how cells migrate and survive in early embryonic development.
In fully developed cells, Zeb1 is normally blocked. But when the factor is reactivated in cancer cells, it allows the tumor cells to disseminate throughout the body and quickly adapt to changing conditions in their microenvironment. This allows them to develop into metastases and form secondary tumors.
“The EMT-TF Zeb1 is a key factor for the formation of precursor lesions, invasion, and notably metastasis,” the authors wrote. “Depletion of Zeb1 suppresses stemness, colonization capacity, and phenotypic/metabolic plasticity of tumor cells, probably causing the observed in vivo effects.
When Zeb1 is inactivated, the cancer cells can no longer adapt to their new environment as easily. This results in the development of a variant of pancreatic cancer, which presents significantly lower metastatic capacity.
“Different EMT-TFs have complementary subfunctions in driving pancreatic tumor metastasis,” the authors concluded. “Therapeutic strategies should consider these potential specificities of EMT-TFs to target these factors simultaneously.”
The authors expressed hope that their findings will lead to the development of new treatment strategies to combat the aggressive nature of pancreatic cancer.