The LKB1 tumor suppressor in women’s cancers

We have shown that the tumor suppressor gene LKB1 gene is frequently mutated in cervical cancer, the first recurring mutation identified in this common and clinically important cancer. Our studies have shown that LKB1 inactivation is associated with particularly aggressive clinical behavior, and may thus warrant more vigorous clinical interventions.

We have also explored the role of LKB1 in endometrial cancer (cancer of the lining of the uterus) in human tumors and with the Sprr2f-Cre transgene that we developed for conditional gene targeting within endometrial epithelium. This work led to an important LKB1-based model of invasive endometrial cancer and to the discovery of a novel immunological mechanism by which LKB1 loss promotes tumor growth via control of the tumor microenvironment.

We are now refining these genetic model systems to further study and understand the role of LKB1 in cancers of the reproductive tract, with the ultimate goal of developing therapies effective against tumors deficient for LKB1.

LKB1 mutations occur across cervical cancer subtypes
MDA=minimal deviation adenocarcinoma
SCC=squamous cell carcinoma