KLF family of proteins in gastrointestinal tumors (Review)

The Krüppel-like family (KLF) are important transcriptional regulators that have important, context-specific roles in gastrointestinal (GI) malignancies. Their roles are very heterogeneous; each of the KLF members may play tumor-suppressive or tumor-promoting roles, depending on the type of tumor, clinical stage and the cellular microenvironment, which fine-tunes the core biological processes of tumor cell proliferation, apoptosis, epithelial-mesenchymal transition and metabolism. This is a context-dependent functional heterogeneity that poses a big challenge in the translation of KLF family transcription factors from basic research into clinical applications. In addition to these classical regulatory functions, KLFs have a key role in the restructuring of the tumor immune microenvironment (TIME). KLFs have the potential to affect the effectiveness of cancer immunotherapy by modulating immune cell infiltration, immune cell functions and immune evasion by tumors. The present review is a systematic review that summarizes the molecular regulatory mechanisms of KLFs in the major GI malignancies, such as colorectal, gastric, liver, esophageal and pancreatic cancer. The present review points to their control of major signaling pathways, including Wnt/β-catenin and PI3K/AKT, and their new roles in the remodeling of TIME. Moreover, the present review assesses their translational utility as diagnostic and prognostic biomarkers and therapeutic targets, and confronts the clinical issues involved in targeting transcription factors, thus giving a theoretical basis for oncology approaches in different types of GI cancer.