Faculty, Staff and Student Publications
Publication Date
7-1-2025
Journal
Cancer Letters
DOI
10.1016/j.canlet.2025.217591
PMID
40054660
PMCID
PMC12040592
PubMedCentral® Posted Date
7-1-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells. By characterizing dynamics in stem-cell crosstalk with the microenvironment along the pseudotime axis, we found differential roles of ANXA1 at different stages of tumor development. In precancerous stages, reduced ANXA1 levels promoted monocyte differentiation toward M1 macrophages and inflammatory responses, whereas during malignant progression, upregulated ANXA1 fostered M2 macrophage polarization and cancer-associated fibroblast transformation by increasing TGF-β production. Our spatiotemporal analysis further provided insights into mechanisms responsible for immunosuppression and a potential target to control evolution of precancer and mitigate the risk for cancer development.
Keywords
Humans, Tumor Microenvironment, Neoplastic Stem Cells, Cell Transformation, Neoplastic, Neoplasms, Cell Differentiation, Macrophages, Transforming Growth Factor beta, Disease Progression
Published Open-Access
yes
Recommended Citation
Luo, Ruihan; Liu, Jiajia; Wang, Tiangang; et al., "The Landscape of Malignant Transition: Unraveling Cancer Cell-of-Origin and Heterogeneous Tissue Microenvironment" (2025). Faculty, Staff and Student Publications. 1753.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/1753
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