High-throughput functional screen identifies YWHAZ as a key regulator of pancreatic cancer metastasis

High-throughput functional screen identifies YWHAZ as a key regulator of pancreatic cancer metastasis

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Abstract Pancreatic cancer is a leading cause of cancer death due to its early metastasis and limited response to the current therapies.Metastasis is a complicated multistep process, which is determined by complex genetic alterations.Despite emtek 2113 the identification of many metastasis-related genes, distinguishing the drivers from numerous passengers and establishing the causality in cancer pathophysiology remains challenging.Here, we established a high-throughput and piggyBac transposon-based genetic screening platform, which enables either reduced or increased expression of chromosomal genes near the incorporation site of the gene search vector cassette that contains a doxycycline-regulated promoter.

Using this strategy, we identified YWHAZ as a key regulator of pancreatic cancer metastasis.We demonstrated that functional activation of Ywhaz by the gene search vector led to enhanced metastatic capability in mouse pancreatic cancer cells.The metastasis-promoting role of YWHAZ was further validated in human pancreatic cancer cells.Overexpression of YWHAZ resulted in more aggressive metastatic phenotypes in vitro bar drain board and a shorter survival rate in vivo by modulating epithelial-to-mesenchymal transition.

Hence, our study established a high-throughput screening method to investigate the functional relevance of novel genes and validated YWHAZ as a key regulator of pancreatic cancer metastasis.