What question did this study set out to answer?

This research aims to explore how TIMP-1 modulation affects angiogenic factors in KRAS-dependent and independent NSCLC cells.

April 5, 2026

Abstract 7477: Angiogenic profile associated with KRAS dependency upon modulation of TIMP1

Key Points

This research aims to explore how TIMP-1 modulation affects angiogenic factors in KRAS-dependent and independent NSCLC cells.
Utilized KRAS-dependent H441 and independent H460 NSCLC cell lines.
Modulated TIMP-1 levels through overexpression and knockout strategies.
Analyzed serum-free conditioned media using angiogenesis proteome profiler array.
Conducted RNA-seq analysis on multiple NSCLC lines.
TIMP-1 overexpression increased pro-angiogenic factors VEGF1 and CXCL8.
TIMP-1 knockdown led to decreased levels of these factors.
A reciprocal expression pattern between TIMP-1 and Thrombospondin-1 was observed.
High c-Myc levels were noted in KRAS-dependent cells, further increased by TIMP-1 overexpression.

Abstract

Abstract Non-small cell lung carcinoma (NSCLC) remains a leading cause of cancer-related deaths, with KRAS mutations conferring oncogene addiction and chemoresistance to therapy. Our previous work demonstrated that Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) inversely correlates with KRAS dependency and promotes epithelial-mesenchymal transition (EMT). Given the role of TIMP-1 in tumor progression, we investigated how TIMP-1 modulation impacts the expression of angiogenic mediators in NSCLC cells.KRAS-dependent (H441) and KRAS-independent (H460) NSCLC cell lines were modulated to overexpress (OE) or knock down (KD) TIMP-1, respectively. Serum free conditioned media from these cells was analyzed using angiogenesis proteome profiler array (R Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7477.

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Cite This Study

M-Thirusenthilarasan et al. (Fri,) studied this question.

synapsesocial.com/papers/69d1fdbfa79560c99a0a409c https://doi.org/https://doi.org/10.1158/1538-7445.am2026-7477

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