1. Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin,150001, China.
2. Bio-Bank of Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
3. Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, 150001, China.
4. Editorial Board of Harbin Medical University, Harbin Medical University, Harbin 150001, China.
5. School of Medicine and Health, Harbin Institute of Technology, Harbin, 150001, China.
6. Heilongjiang Key Laboratory of Children Development and Genetic Research, Harbin Medical University, Harbin,150001, China.
7. School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150001, China.
8. Drug Engineering and Technology Research Center, Harbin University of Commerce, Harbin, 150001, China.
9. St John's College William Nicholls Drive, Old St Mellons, Cardiff, CF35YX, United Kingdom.
* These authors contributed equally.
Colon adenocarcinoma (COAD) is the most common malignancy of the digestive tract, which is characterized by a dismal prognosis. No effective treatment has been established presently, thus there is an urgent need to understand the mechanisms driving COAD progression in order to develop effective therapeutic approaches and enhance clinical outcomes. In this study, we found that KLF7 is overexpressed in COAD tissues and correlated with clinicopathological features of COAD. Both gain-of-function and loss-of-function experiments have unequivocally demonstrated that overexpression of KLF7 promotes the growth and metastasis of COAD in vitro and in vivo, while KLF7 knockdown attenuated these effects. Mechanistically, our findings reveal that KLF7 can specifically bind to the promoter region of PDGFB (TGGGTGGAG), thus promoting the transcription of PDGFB and increasing its secretion. Subsequently, secreted PDGFB facilitates the progression of COAD by activating MAPK/ERK, PI3K/AKT, and JAK/STAT3 signaling pathways through PDGFRβ. Additionally, we found that sunitinib can block PDGFB signaling and inhibit COAD progression, offering a promising therapeutic strategy for COAD treatment.
Keywords: Colon adenocarcinoma, KLF7, PDGFB, Sunitinib