FOXM1 drives brain metastases formation of colorectal cancer

Colorectal cancer (CRC) is currently the fourth leading etiology of brain metastasis (BM). Yet, mechanisms supporting the formation of CRC BM are mostly unknown. In order to identify drivers that lead to tropism and adaptation of CRC cells to the brain environment, we compared the transcriptome of BM to liver metastases (LM, n=6) obtained from patients with CRC (n=9). In order to minimize heterogeneity, we focused on KRAS-mutated tumors only. We noted differential expression of 9 genes, among them the transcription factor Forkhead box protein M1 (FOXM1). Analysis of FOXM1 expression in clinical samples, using IHC validated increased expression in BM compared to LM. Studies in mice indicated increased FOXM1 levels in CRC cells transplanted in mice brain. Similarly, FOXM1 expression increased in CRC cells grown in astrocytes conditioned media compared to those grown in hepatocyte conditioned media. FOXM1 is a transcription factor that is involved in early development, proliferation, differentiation, cell cycle advancement and more. In CRC, FOXM1 has a role in tumor initiation and progression. These data indicate FOXM1 as a novel player mediating CRC BM formation and may pave the way for novel treatment strategies for the treatment of CRC BM.