Cancer 'stemness' regulator

The protein FOXK2 promotes the survival of ovarian cancer stem cells, according to a Northwestern Medicine study published in the Journal of Clinical Investigation

According to Daniela Matei, MD, blocking this protein can reduce cancer recurrence after initial treatment

"If you use inhibitors to this pathway, the cancer stem cells will die instead of regenerating the tumor," said Matei, who is also a professor of medicine in the Division of Hematology and Oncology

If treated early, ovarian cancer often follows a predictable course of remission after chemotherapy and recurs two years later

In the current study, Matei and her collaborators compared gene expression in ovarian CSCs and normal ovarian cancer cells, looking for genes that were highly expressed in CSCs

The researchers, including first author Yaqi Zhang, a student in the Driskill Life Sciences Graduate Program (DGP), found that FOXK2 directly regulates IREI-alpha, a key sensor that activates the unfolded protein response (UPR)

External stressors to cells—in CSCs, chemotherapy or hypoxia when cells aggregate—can cause protein misfolding

Blocking FOXK2 expression in CSCs, in turn, reduces the activation of UPR-inhibited CSC growth, reducing their so-called "stemness" and making them more like normal cells

These findings represent a possible way to target CSCs in tumors, Matei said

"We are very interested in new inhibitors of this pathway," Matei said

Courtesy of Northwestern University