Graduation Date

Fall 12-19-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Biochemistry & Molecular Biology

First Advisor

Imayavaramban Lakshmanan, PhD

Second Advisor

Sushil Kumar, PhD

Third Advisor

Moorthy Palanimuthu Ponnusamy, PhD

Abstract

Lung adenocarcinoma (LUAD) remains one of the deadliest cancers globally, mainly due to its aggressive metastatic potential. Emerging evidence implicates extracellular matrix (ECM) remodeling as a critical driver of tumor progression. In this study, we investigate the cooperative roles of the MUC16 and COL7A1 genes, which are frequently overexpressed in LUAD, in ECM remodeling, stiffness, and metastatic progression.

It was hypothesized that the overexpression of MUC16 and COL7A1 increases ECM stiffness, thereby triggering integrin-mediated signaling cascades that support tumor cell invasion and dissemination. Transcriptomic analysis of LUAD patient datasets revealed a significant co-upregulation of MUC16 and COL7A1 in metastatic tumors. Functional assays in 3D ECM-mimetic cultures demonstrated that co-expression leads to increased collagen deposition and matrix crosslinking, resulting in a stiffer ECM microenvironment.

Furthermore, this hypothesized remodeling enhances integrin β1 activation and downstream FAK/Src signaling, promoting cytoskeletal rearrangements and migratory phenotypes. In vivo models confirmed that dual overexpression accelerates metastatic burden compared to single-gene overexpression or controls. These findings suggest that MUC16 and COL7A1 act synergistically to remodel the ECM in LUAD, creating a mechanically favorable niche for tumor spread. Targeting this axis may offer novel therapeutic opportunities to hinder metastasis and improve patient outcomes.

Comments

2025 Copyright, the authors

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