Comparative Analysis of Stk11/Lkb1 Versus Pten Deficiency in Lung Adenocarcinoma Induced by CRISPR/Cas9

• Main Authors: Martin F. Berthelsen, Siv L. Leknes, Maria Riedel, Mette A. Pedersen, Justin V. Joseph, Henrik Hager, Mikkel H. Vendelbo, Martin K. Thomsen
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: Cancers
• Subjects: lung cancer; CRISPR; adenocarcinoma; mouse model; STK11; PTEN
• Online Access: https://www.mdpi.com/2072-6694/13/5/974

This study focused on STK11, PTEN, KRAS, and TP53, which are often found to be mutated in lung cancer. We compared Stk11 and Pten implication in lung cancer in combination with loss of Trp53 and gain of function of Kras in a CRISPR/Cas9 mouse model. Mice with loss of Stk11, Trp53, and KrasG12D mutation (SKT) reached human endpoint at around four months post-initiation. In comparison, mice with loss of Pten, Trp53, and KrasG12D mutation (PKT) survived six months or longer post-initiation. Pathological examination revealed an increase in proliferation in SKT deficient lung epithelia compared to PKT. This difference was independent of Pten loss, indicating that loss of Pten is dispensable for cell proliferation in lung adenocarcinoma. Furthermore, tumors with loss of Stk11, Trp53, and KrasG12D mutation had a significantly higher progression rate, monitored by PET/MRI scanning, compared to mice with loss of Pten, Trp53, and KrasG12D mutation, revealing that mutations in Stk11 are essential for adenocarcinoma progression. Overall, by using the CRISPR/Cas9 mouse model of lung adenocarcinoma, we showed that mutations in Stk11 are a key driver, whereas loss of Pten is dispensable for adenocarcinoma progression.