Abstract
Colorectal cancer(CRC) is one of the most commonly diagnosed cancers in human beings and metastasis is the main death reason. Recently, Gli1 has been reported to be a key regulator of various cancer biologies and genes expressions. However, the detailed molecular mechanism of Gli1 in CRC metastasis remains largely unknown. In this study, we aimed to investigate the role of Gli1 in CRC metastasis. We used qRT-PCR, Immunohistochemistry and Western blot to test the expression levels of Gli1, Foxm1 and other target genes in the tissues and cells; Lentivirus stable transfection to change the expression levels of Gli1 and Foxm1; Wound-healing, cell invasion, migration assays and tail vein metastatic assay to test the role of Gli1 in CRC metastasis in vitro and vivo. We demonstrated that Gli1 was significantly overexpressed in colorectal cancer tissues and cells. Foxm1 level had a positive correlation with Gli1. Furthermore, we found that Gli1 promotes colorectal cancer cells metastasis in a Foxm1-dependent manner by activating EMT and PI3K-AKT signaling. Thus, we proved that Gli1 plays important role in CRC metastasis and provided a new visual field on the therapy of CRC metastasis.
Highlights
Colorectal cancer is the third most commonly diagnosed cancer in males and the second in females [1]
We found that Gli1 expression had a close correlation with the metastasis factors:higher in patients with nodal metastasis than in those with no metastasis (86.2% vs 67.6%, P = 0.02); higher in patients with advanced stage disease than in those with earlystage (84.7% vs 68.7%, P = 0.038)
We addressed whether integration of the Gli1-Foxm1 axis and epidermal growth factor receptor (EGFR)-phosphatidylinositol 3 kinase (PI3K)-AKT pathway is a critical step in colorectal cancer metastasis
Summary
Colorectal cancer is the third most commonly diagnosed cancer in males and the second in females [1]. A large amount of these patients are initially diagnosed with developed stage IV CRC [2], and the underlying mechanism has not been understood well [3]. It is generally accepted that metastasis is the main cause of death in patients with CRC due to the tumor resistance to conventional therapies and a poor overall survival [4, 5]. To find the biomarkers of CRC metastasis for its targeted therapy and prognosis is urgently required for clinical medicine. Hedgehog (Hh) signaling pathway plays a critical role in normal cellular development including embryogenesis, tissue patterning, and differentiation [6]. In the canonical pathway progression, Hh ligand binds to Ptch and releases its tonic inhibition of Smo
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