Associate Professor Everardo Macias, PhD, was invited to give a talk titled “Mechanistic and Therapeutic Evaluation of Hippo Tumor Suppressor STK3 in Hormone Dependent Cancers” at Michigan State University (MSU) Department of Physiology in East Lansing on Jan. 30, 2025.
STK3 and STK4 (aka MST2/4) are core hippo tumor suppressor kinases, which are part of a signaling pathway in cells that helps control cell growth and prevent cancer. In most normal cells, they inhibit cell growth by initiating a signaling cascade that inhibits the cell growth activity of YAP1/TAZ co-transcription factors. In most cancer types STK3/4 are lost, leading to activation of YAP/TAZ.
Counter to this widely accepted dogma, the Macias lab observed that the STK3 gene is amplified in prostate and breast cancers. Other groups also have now found it increased in gastric cancers and leukemias. In a series of published papers, the Macias lab has shown that STK3 plays a new role in promoting the growth of prostate and breast cancer.
Macias collaborated with medicinal chemist David Drewry, PhD, at the University of North Carolina at Chapel Hill’s Eshleman School of Pharmacy to identify lead compounds to inhibit STK3 and have anti-proliferative effects on prostate and breast cancer cells. On the other hand, inhibiting STK3 with lead compounds in normal cells such as cardiomyocytes induced proliferation and protected them against the effects of chemotherapies such as doxorubicin. In new unpublished studies presented at MSU, the Macias lab described use of an integrated-omics approach to better understand how STK3 signaling pathways and mechanisms affect prostate cancer.
He based his talk on new research currently in submission and on two previous publications: