PTEN-FOXO1 in Prostate Cancer

The Cancer Epigenetics and Functional Genomics Lab at Mayo Clinic investigates the mechanisms of PTEN-FOXO1 tumor suppressors in prostate cancer survival and metastasis.

PTEN is one of the most frequently mutated or deleted tumor suppressor genes in prostate cancer. Dr. Huang's research team is interested in defining molecular mechanisms by which loss of PTEN leads to inhibition of the forkhead nuclear factor FOXO1, thereby promoting prostate cancer cell proliferation, survival, metastasis and resistance to cancer therapies.

In addition to the functional loss of FOXO1 due to protein phosphorylation, FOXO1 is often deleted in human prostate cancer. Moreover, TMPRSS2-ERG gene fusion — juxtaposing the androgen-responsive TMPRSS2 gene promoter with the oncogenic ETS-family transcription factor ERG — results in aberrant overexpression of ERG in approximately 50 percent of all human prostate cancer.

Dr. Huang's lab uses biochemical, mouse genetic and bioinformatics approaches to understand how FOXO1 loss works in concert with TMPRSS2-ERG fusion to drive prostate tumorigenesis and metastasis. Findings from this project could help researchers identify new therapeutic targets for effective treatment of TMPRSS2-ERG-positive tumors.

The Cancer Epigenetics and Functional Genomics Lab's PTEN-FOXO1 research project is funded by R01 grants from the National Cancer Institute.