KLF11 in Extracellular Vesicles Derived from adMSCs Inhibits Colorectal Cancer via Suppressing SOAT1-Mediated...

Area of Science:

• Oncology
• Stem Cell Biology
• Molecular Biology

Background:

• Colorectal cancer (CRC) is a leading cause of cancer mortality.
• Adipose-derived mesenchymal stem cells (adMSCs) and their secreted extracellular vesicles (EVs) show potential in retarding CRC progression.

Purpose of the Study:

• To elucidate the mechanism by which adMSCs-EVs influence CRC progression.
• To investigate the role of Krüppel-like factor 11 (KLF11) within adMSCs-EVs in CRC.

Main Methods:

• Analysis of KLF11 expression in adMSCs-EVs.
• In vitro and in vivo experiments using adMSCs-EVs and KLF11-depleted adMSCs-EVs (adMSCs-EVs^sh-KLF11).
• Investigation of the PI3K/AKT signaling pathway and sterol o-acyltransferase 1 (SOAT1) expression.

Main Results:

• KLF11 was upregulated in adMSCs-EVs.
• adMSCs-EVs^sh-KLF11 promoted CRC cell lipogenesis, viability, proliferation, migration, invasion, and accelerated tumor growth.
• adMSCs-EVs-derived KLF11 suppressed the PI3K/AKT pathway by repressing SOAT1 transcription.
• SOAT1 knockdown mimicked the pro-tumorigenic effects of adMSCs-EVs^sh-KLF11.

Conclusions:

• KLF11 delivered by adMSCs-EVs inhibits CRC progression.
• The mechanism involves the inactivation of the PI3K/AKT signaling pathway via transcriptional downregulation of SOAT1.
• This process suppresses lipogenesis and malignant behaviors in colorectal cancer cells.