Dynamin 1 promotes colorectal cancer progression by activating the PI3K/Akt signaling pathway

Uncontrolled proliferation, local invasion, and distant metastasis are hallmarks of malignancies, and they play crucial roles in tumor progression. Dynamin 1 (DNM1) is a member of the dynamin guanosine-5′-triphosphatease (GTPase) subfamily that regulates membrane fission, cytokinesis, and vesicle secretion. However, its function in colorectal-cancer (CRC) progression remains unclear. We used public datasets and a tissue microarray (TMA) cohort to analyze differential expression of DNM1 between CRC tissues and adjacent nontumor tissues (NTs). The role of DNM1 in CRC cells was determined by in vitro experiments, including colony formation, Cell Counting Kit-8 (CCK-8), and Transwell assays. Ribonucleic acid sequencing (RNA-seq) and bioinformatics analysis were performed to investigate mechanisms that DNM1 may be involved in. KLF5 was identified as an upstream transcriptional activator of DNM1 through a combination of bioinformatic screening and functional experiments. Xenograft and metastatic models were established to investigate the effects of DNM1 on tumor growth and metastasis. We found that DNM1 expression was upregulated in CRC tissues, which significantly correlated with poor patient prognoses. DNM1 overexpression (OE) enhanced the proliferation, migration, and invasion capabilities of CRC cells both in vitro and in vivo, whereas DNM1 knockdown (KD) yielded the opposite results. Mechanistically, we identified Krüppel-like factor 5 (KLF5) as an upstream transcription factor that activates DNM1 transcription. Furthermore, DNM1 was shown to mediate the activation of epithelial–mesenchymal transition (EMT) and the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. DNM1 promotes CRC progression and malignant phenotypes, and targeting the KLF5/DNM1/Akt axis may represents a promising strategy to improve patient outcomes.