KLF4在乳腺癌中的表达调控和生物学功能研究

KLF4为锌指结构转录因子SP/KLF家族成员，在多种不同的生理过程中发挥重要作用，包括发育、分化和维持内环境稳定等。KLF4可以与不同的转录辅助因子相结合，从而对下游靶基因产生不同的转录调控作用。KLF4的表达调控、生物学功能和分子机制存在高度的组织结构特异性，并受到多种因素的影响，具有癌基因和抑癌基因双重活性。此外，KLF4还能诱导多能干细胞的形成和间质上皮转化（MET），从而对肿瘤生物学行为及机理的研究具有重要的作用和深远的意义。本研究旨在前期工作的基础上，系统深入地研究KLF4在乳腺癌中的表达调控、对肿瘤微环境和细胞表型的影响及其潜在的分子机制等，从而明确 KLF4在乳腺癌中表达水平及其调控机制，以及相关的生物学功能和涉及的分子机理，继而进一步阐明KLF4在乳腺癌发生发展中的作用，为提高乳腺癌的诊断水平，实现个体化和靶向治疗以及预后评估奠定分子基础和提供新的手段和方法。

KLF4 is a bi-functional transcription factor that can either activate or repress transcription, depending on the target gene, and utilizing different mechanisms. KLF4 can function as an oncogene or a tumor suppressor depending on the type of cancer involved. Moreover, KLF4 is not only important in reprogramming differentiated fibroblasts into inducible pluripotent stem cells, which highly resemble embryonic stem cells, but also as a key regulator of monocytic differentiation and a potential target for translational immune modulation. Finally, MEFs null for the klf4 alleles are genetically unstable, support a crucial role for KLF4 in maintaining genetic stability and as a regulator in tumor milieu. In this study, we will explore the potent role of KLF4 in mammary tumorigenesis and at the nexus between chronic inflammation and cancer associated fibroblast (CAF). Thus, we may provide an effective therapeutic approach to suppress tumorigenicity in breast cancer by targeting KLF4.