Abstract A44: Inhibition of Foxm1 transcription factor diminished Kras-mutated tumor development

Increased expression level of the Forkhead Box M1 (FOXM1) transcription factor is found in multiple types of cancers, and its expression is correlated with poor prognosis in patients with cancers, including non-small cell lung cancers and pancreatic cancers. We and others have shown that FoxM1 transcriptionally regulates a variety of genes essential for cell cycle progression, inflammation, angiogenesis, tumor cell invasiveness and survival. Published studies demonstrated that genetic deletion of Foxm1 gene from SPC-rtTA/tetO-KrasG12D/Foxm1 fl/fl mouse lung epithelial cells conferred resistance to tumorigenesis caused by oncogenic KrasG12D, indicating Foxm1 is a critical regulator of Kras signaling pathway during lung cancer initiation. When treated SPC-rtTA/tetO-KrasG12D/tetO-FOXM1 mice with Doxycycline, lung epithelial cell-specific expressed transgenic FOXM1 and Kras cooperate to promote tumor growth in mouse lungs. In the present study, we determine whether expression of FoxM1 affects proliferation of human cancer cells harboring oncogenic Kras. Here, we show that depletion of FOXM1 expression using inducible shFOXM1 diminished proliferation of Kras-mutated human non-small cell adenocarcinoma (A549 and NCI-H23) and pancreatic cancer (PANC-1 and AsPC-1) cell lines. In contrast, increased expression of FOXM1 caused increased proliferation of Kras mutated cancer cells. Scratch wound healing assay demonstrated that FOXM1 stimulates the migration of these cells, which is associated with elevated epithelial-mesenchymal transition (EMT) markers. Our studies demonstrate that FOXM1 transcription factor is required for Kras mutated human cancer cells proliferation during tumor progression. Citation Format: I-Ching Wang, Hsin Chih Chien, Sheng-Yang Chao, Chien-Cheng Li. Inhibition of Foxm1 transcription factor diminished Kras-mutated tumor development. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A44.