Abstract
GRHL3 is a factor associated with a tumor, of which the molecular mechanism remains a further investigation. We explored the underlying mechanism of tumor-promoting effect of GRHL3 in colorectal cancer (CRC), which is involved in the MEK1/2 pathway. The expression of GRHL3 was measured in CRC and adjacent normal tissue using qPCR and immunohistochemical staining. Lentivirus-mediated knockdown expression of GRHL3 was performed in the CRC cell line HT29. Cell proliferation and metastasis were assayed in vitro, and tumorigenicity was investigated in vivo. We found higher GRHL3 expression in colorectal cancer, which was negatively correlated with patients' prognosis. Results from studies in vitro and in vivo indicated that downregulation of GRHL3 expression inhibited tumor growth and metastasis and inhibited the activation of the MEK1/2 pathway. The effect of GRHL3 downexpression was the same as that of MEK1/2 antagonists on suppression of tumor growth and metastasis. Our results suggested that GRHL3 may act as an oncogene to promote tumor growth and metastasis via the MEK pathway in colorectal cancer.
Highlights
As one of the most common malignancies, colorectal cancer (CRC) is responsible for approximately 6 hundred thousand deaths per year worldwide [1]
We explored the role of GRHL3 in tumor migration and invasion and poor overall survival rate involved in progression and prognosis in CRC, which may serve as a potential target for the treatment of CRC
Our results suggested that GRHL3 mediates the tumor metastasis
Summary
As one of the most common malignancies, colorectal cancer (CRC) is responsible for approximately 6 hundred thousand deaths per year worldwide [1]. Grainyhead (GRH) is the first member of the transcription factor family including Grainyhead-like (GRHL) proteins [3]. It has been shown that GRHL family factors play a significant role in the mechanics-related processes of embryonic neural tube closure, epidermal formation, and wound healing [4,5,6,7,8]. GRHL3, known as Get, is reported to play an essential role in epidermal barrier formation, wound healing, and neural tube closure [5]. GRHL3-/- mice are born with neural tube closure and eye-open defects [6, 10]. Mice with conditional deletion of GRHL3 were found to develop skin tumors spontaneously with age and show increased susceptibility to carcinogenic chemicals in SCC [13, 14]. Higher expression of GRHL3 is measured in the early stages of breast cancer; significantly reduced expression in advanced stages of breast
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