KLF8 is activated by TGF‐β1 via Smad2 and contributes to ovarian cancer progression. Issue 5 (16th March 2022)

• Record Type: Journal Article
• Authors: Cherukunnath, Aparna; Davargaon, Ravichandra S.; Ashraf, Rahail; Kamdar, Urja; Srivastava, Amit K.; Tripathi, Prem P.; Chatterjee, Nabanita; Kumar, Sanjay
• Is Part Of: Journal of cellular biochemistry. Volume 123:Issue 5(2022)
• Page Start: 921
• Page End: 934
• Publication Date: 2022-03-16
• Subjects: EMT -- invasion -- KLF8 -- ovarian cancer -- Smad2 -- TGF‐β1; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.30235
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Krüppel‐like factor 8 (KLF8) is a transcription factor expressed abnormally in various cancer types and promotes oncogenic transformation. However, the role of KLF8 in ovarian cancer (OC) progression remains unclear. This study reports that transforming growth factor‐β1 (TGF‐β1)/Smad2/KLF8 axis regulates epithelial–mesenchymal transition (EMT) and contributes to OC progression. We analyzed the KLF8 expression in OC cells and tissues, wherein a significant overexpression of KLF8 was observed. Increased KLF8 expressions were correlated with higher cell proliferation, EMT, migration, and invasion and conferred poor clinical outcomes in OC patients. Overexpressed KLF8 increases F‐actin polymerization and induces cytoskeleton remodeling of OC cells. Furthermore, a dissection of the molecular mechanism defined that TGF‐β1 triggers KLF8 through the Smad2 pathway and regulates EMT. Pharmacological and genetic inhibition of Smad2 followed by TGF‐β1 treatment failed to activate KLF8 expression and induction of EMT. Using promoter‐luciferase reporter assays, we defined that upon TGF‐β1 activation, phosphorylated Smad2 binds and promotes the KLF8 promoter activity, and knockdown of Smad2 inhibits KLF8 promoter activation. Together, these results demonstrate that TGF‐β1 activates KLF8 expression by the Smad2 pathway, and KLF8 contributes to OC progression and may serve as a potential therapeutic strategy for treating OC patients.