Epigenetic Factors Promoting Pancreatic Cancer Aggressiveness Identified

Pancreatic cancer cells. Credit: Anne Weston, London Research Institute, CRUK
Researchers from Genentech have identified an epigenetic transcription regulator that appears to influence how aggressive pancreatic cancer cells are. When the regulator, a histone methyltransferase called SUV420H2, was repressed, it was found to promote epithelial-like properties in cancer cells, reducing their motility and invasiveness and making them more susceptible to chemotherapy.

The research team wanted to investigate whether or not epigenetics could be responsible for the epithelial-to-mesenchymal transition by altering gene expression.
To do so, they screened 300 epigenetic factors to observe the effect they had on the cellular state. Their screen revealed that when SUV420H2 was reduced, the cancer cells began to regain some epithelial characteristics once more, such as reduced motility and invasiveness. Notably, the team also found that SUV420H2 inhibition increased the cancer’s sensitivity to two of the most common chemotherapy drugs used to treat pancreatic cancer, 5-fluorouracil and gemcitabine.

“Collectively, these results indicated that SUV420H2 is a potent epigenetic factor in controlling epithelial/mesenchymal identity status in pancreatic cancer cells, and its repression elicits a global MET from a molecular standpoint,” the authors concluded.
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