2020/03/27 by Ivana Heřmanová, Patricia Zúñiga-García, Alfredo Caro‐Maldonado +32 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Medicine · #Cancer-related gene regulation #Genetic factors in colorectal cancer #Prostate Cancer Treatment and Research
paper · pdf · doi:10.1084/jem.20191787
openalex publication_date 2020/03/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
Gene dosage is a key defining factor to understand cancer pathogenesis and progression, which requires the development of experimental models that aid better deconstruction of the disease. Here, we model an aggressive form of prostate cancer and show the unconventional association of LKB1 dosage to prostate tumorigenesis. Whereas loss of Lkb1 alone in the murine prostate epithelium was inconsequential for tumorigenesis, its combination with an oncogenic insult, illustrated by Pten heterozygosity, elicited lethal metastatic prostate cancer. Despite the low frequency of LKB1 deletion in patients, this event was significantly enriched in lung metastasis. Modeling the role of LKB1 in cellular systems revealed that the residual activity retained in a reported kinase-dead form, LKB1K78I, was sufficient to hamper tumor aggressiveness and metastatic dissemination. Our data suggest that prostate cells can function normally with low activity of LKB1, whereas its complete absence influences prostate cancer pathogenesis and dissemination.