Unravelling the Role of TGFBI in Cancer-Associated Fibroblasts and Tumor Microenvironment of NSCLC

*Corresponding author: (e-mail: [e-mail]).

Abstract

Background: Our RNA sequencing analysis on NSCLC patient-derived cancer-associated fibroblasts has identified TGFBI/BigH3, an ECM binding protein downstream of the TGF-β pathway, significantly upregulated in CAF. This project aims to elucidate the intricate crosstalk between tumor cells and the lung stroma, focusing on the pivotal role of TGFBI in CAF activation.

Materials and Methods: To explore TGFBI's impact on maintaining CAF properties, we are utilizing functional assays such as Collagen contraction, Transwell migration, Contact Dependent Co-culture, and Contact Independent Co-culture. We have also generated Lentiviral-mediated shTGFBI knockdown CAF cells and performed bulk RNA sequencing to understand the mechanism better.

Results: Upon knockdown of TGFBI in CAF, we observe a loss in function properties such as contractility and migration. Conditioned media and contact-dependent co-culture experiments have revealed an increase in levels of TGFBI and ACTA2 in both Normal and Cancer-associated Fibroblasts.

Conclusion: Preliminary findings have yielded compelling evidence suggesting that TGFBI plays an indispensable role in maintaining the functional attributes of CAFs. By dissecting the interplay between TGFBI and CAFs, this study aims to provide valuable insights that could inform the development of targeted therapies for NSCLC.

Publication History

Article published online:
08 July 2024