Investigating the Role of KLF6-SV1 as a Regulator of EMT Progression

Post-translational modifications (PTMs) are crucial for all biological processes and offer insights into protein functions, including their activity state, subcellular location, solubility, folding, trafficking, and protein−protein interactions. Amino acids modified by PTMs act as molecular switches, influencing protein function and characteristics, and increasing proteome complexity. Krüppel-like transcription factors (KLFs) are a family of transcription factors that regulate essential cellular processes such as proliferation, differentiation, migration, programmed cell death, and various cancer-relevant pathways. In this study we investigated the effect of phosphorylation on the binding affinity and stability of KLF6-SV1 (Krüppel-like factor 6 splice variant 1) interactions with its binding partners, potentially revealing a mechanism for its oncogenic activity. KLF6-SV1 and binding partners interactions were computationally analyzed to evaluate the role of phosphorylation in KLF6-SV1 on their binding affinity and stability. In the present study, it was found that despite a decrease in the binding force between KLF6-SV1 and TWIST1, KLF6-SV1 and MMP9, KLF6-SV1 and SNAI1 upon phosphorylation, the overall energy of each complex decreased, resulting in increased stability. This suggests that phosphorylation plays a significant role in activating KLF6-SV1 and its partner’s oncogenic activities by making the complex stable. This study provides valuable insights into the underlying molecular mechanism of cancer pathogenesis and suggests that KLF6-SV1 phosphorylation is one of the critical events in cancer pathogenesis.