Macrophages are very important immune cells and play critical roles in tumour immunity. Macrophage subtypes can be divided into classical polarization (M1 macrophages) and alternative polarization (M2 macrophages) under different microenvironments. Krüppel-like factor 4 (KLF4) is an essential transcription factor for macrophage polarization. Our previous study has shown that KLF4 SUMOylation plays an important role in macrophage M2 polarization. In the present study, small ubiquitin-like modifier (SUMO) specific peptidase (SENP)1 was identified as a specific protease for KLF4 de-SUMOylation, with the SENP1-KLF4 axis playing a vital role in M1 macrophage polarization by affecting the nuclear factor kappa B signalling pathway. Additionally, the activity of tumour cells was weakened by KLF4 SUMOylation deficient macrophages. Hence, the SENP1-KLF4 axis is considered to play a crucial role in regulating lipopolysaccharide-induced macrophage M1 polarization, thereby affecting the activity of tumour cells. Therefore, the SENP1-KLF4 axis has therapeutic potential as a target in cancer therapy.
Keywords: KLF4; SENP1; SUMOylation; macrophage polarization.
© 2022 Federation of European Biochemical Societies.