NESPRIN-4 AND SCD1 IN CANCER INVASION

Abstract

Mechanotransduction allows cells to sense and respond to the external environment and regulate cell functions including proliferation, migration, and development. Lipid metabolism also contributes to these processes; however, the intersection between mechanotransduction and lipid regulation remains poorly understood. Specifically, how LINC complexes influence lipid metabolism is unclear. In this study, we investigate the role LINC complex component Nesprin-4 plays in regulating the SREBP1c–SCD1 axis. Our results show that in HepG2 cells, Nesprin-4 knockdown reduced SCD1 expression via SREBP1c and was associated with decreased lipid accumulation, as measured by LipiORDER analysis. We further found that Nesprin-4–mediated regulation of SCD1 influences cell proliferation, potentially through Cyclin D1. In contrast, breast cancer cell lines showed no direct interaction between Nesprin-4 and the SREBP1c–SCD1 axis at the mRNA or protein level. However, consistent with previous findings, loss of Nesprin-4 reduced 3D invasion, and SCD1 overexpression partially rescued this phenotype in breast cancer cell lines. Together, these results suggest a tissue-specific mechanism of Nesprin-4 in linking mechanotransduction and lipid metabolism. This work highlights SCD1 as a potential therapeutic avenue to explore in cancers with dysregulated LINC complex signalling.

Date of Award	2026
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences