The Role of Gut-Enriched Krüppel-Like Factor (GKLF)/ KLF4 in Gastrointestinal Tract-Related Cancers

Abstract

Gut-enriched Kruppel-like factor (GKLF), also called KLF4, is a zinc finger transcription factor, highly expressed in the epithelium and regulates cell proliferation, differentiation, development and apoptosis. KLF4 plays diverse roles in different cancers, functioning as a tumor suppressor or an oncogene. It has been shown that overexpression of KLF4 has led to decreased cancer cell growth through down-regulating cyclin D1 and increased p21, resulting in cell cycle arrest and thus acting as a tumor suppressor. Conversely, the knockdown of KLF4 expression restored cancer cell growth. In addition, KLF4 up-regulates E-cadherin expression to inhibit epithelial- mesenchymal transition (EMT) in mammary epithelial cells and breast cancer cells in vitro. Recently, many studies have revealed that a lower expression of KLF4 was observed in gastrointestinal tract-related tumors, including esophageal squamous cancer, gastric cancer, hepatocellular carcimona (HCC), ductal pancreatic carcinoma and colon cancer. In contrast, increased KLF4 expression was detected in oral squamous cell carcinoma and ductal carcinoma of the breast, promoting aggressive phenotype as an oncogene. These results indicated KLF4 and related signal transduction pathways have the potential to become diagnostic markers and/or therapeutic targets in gastrointestinal track related cancers.