Matrix-state switching in osteosarcoma under therapeutic pressure: integrin rewiring, residual disease, and pulmonary niche adaptation
- 1Trauma Orthopedics Center, Ningbo No.6 Hospital, Ningbo, Zhejiang, China
- 2Ningbo Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation, Ningbo, Zhejiang, China
Abstract
Osteosarcoma cells encounter distinct extracellular environments during primary growth, treatment, detachment, and pulmonary colonization. A single constitutive extracellular-matrix (ECM)–integrin–FAK–AKT pathway therefore cannot explain residual disease and metastasis. This Review proposes matrix-state switching as a stage-resolved framework jointly defined by ligand presentation, adhesion-receptor usage, matrix-coupled signaling dependencies, and the cellular compartment sustaining these interactions. The framework is not an obligatory linear trajectory: observed state differences may reflect reversible adaptation, selection of pre-existing populations, therapy-associated remodeling, or combinations thereof. Primary lesions show component-selective matrix-conditioned drug tolerance; detached cells can preserve Src-dependent PI3K–AKT survival despite loss of sustained FAK and paxillin phosphorylation; and pulmonary colonization introduces distinct tumor-cell and stromal dependencies, including β4–ezrin-associated signaling and the CXCL14–α11β1 fibroblast circuit. Recent single-cell and spatial studies further indicate therapy-associated ECM remodeling and residual malignant-cell programs involving stemness, epithelial–mesenchymal transition, ECM interaction, and PI3K signaling, but do not establish same-clone longitudinal switching. LAMC1 is evaluated strictly as a hypothesis-generating matrix-state candidate because current osteosarcoma-specific evidence remains transcript-level. We position matrix-state switching as a matrix- and adhesion-focused layer within the broader communication-driven osteosarcoma ecosystem and define falsifiable criteria for distinguishing functional state dependencies from association.
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BibTeX
@article{gu2026matrixstate,
title = {{Matrix-state switching in osteosarcoma under therapeutic pressure: integrin rewiring, residual disease, and pulmonary niche adaptation}},
author = {Yang Gu and Yunqiang Zhuang and Wei Zhang},
journal = {Frontiers in Cell and Developmental Biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1987843},
url = {https://doi.org/10.3389/fcell.2026.1987843},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Matrix-state switching in osteosarcoma under therapeutic pressure: integrin rewiring, residual disease, and pulmonary niche adaptation
AU - Yang Gu
AU - Yunqiang Zhuang
AU - Wei Zhang
PY - 2026
DA - 2026/10/22
JO - Frontiers in Cell and Developmental Biology
DO - 10.3389/fcell.2026.1987843
UR - https://doi.org/10.3389/fcell.2026.1987843
AB - Osteosarcoma cells encounter distinct extracellular environments during primary growth, treatment, detachment, and pulmonary colonization. A single constitutive extracellular-matrix (ECM)–integrin–FAK–AKT pathway therefore cannot explain residual disease and metastasis. This Review proposes matrix-state switching as a stage-resolved framework jointly defined by ligand presentation, adhesion-receptor usage, matrix-coupled signaling dependencies, and the cellular compartment sustaining these interactions. The framework is not an obligatory linear trajectory: observed state differences may reflect reversible adaptation, selection of pre-existing populations, therapy-associated remodeling, or combinations thereof. Primary lesions show component-selective matrix-conditioned drug tolerance; detached cells can preserve Src-dependent PI3K–AKT survival despite loss of sustained FAK and paxillin phosphorylation; and pulmonary colonization introduces distinct tumor-cell and stromal dependencies, including β4–ezrin-associated signaling and the CXCL14–α11β1 fibroblast circuit. Recent single-cell and spatial studies further indicate therapy-associated ECM remodeling and residual malignant-cell programs involving stemness, epithelial–mesenchymal transition, ECM interaction, and PI3K signaling, but do not establish same-clone longitudinal switching. LAMC1 is evaluated strictly as a hypothesis-generating matrix-state candidate because current osteosarcoma-specific evidence remains transcript-level. We position matrix-state switching as a matrix- and adhesion-focused layer within the broader communication-driven osteosarcoma ecosystem and define falsifiable criteria for distinguishing functional state dependencies from association.
SN - 2296-634X
ER -