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Publication : A mechanistic basis for the malignant progression of salivary gland tumors.

First Author  Taniguchi S Year  2021
Journal  iScience Volume  24
Issue  12 Pages  103508
PubMed ID  34934927 Mgi Jnum  J:349044
Mgi Id  MGI:7645997 Doi  10.1016/j.isci.2021.103508
Citation  Taniguchi S, et al. (2021) A mechanistic basis for the malignant progression of salivary gland tumors. iScience 24(12):103508
abstractText  Salivary gland tumors are diverse neoplasms, likely reflecting differences in the tissue- and cell-of-origin. 80%-90% of tumors arising in the sublingual gland (SLG) are malignant, whereas the other major glands often form benign tumors. Owing to the lack of experimental models to explore the etiology of salivary gland tumors, the cellular and molecular bases of malignancy remain unknown. Here, we generated a murine model of HRAS(G12V)-driven salivary gland tumors amenable to examine tumor onset and malignant progression. We found that HMGA2 marks the tumor onset, and transformed-SOX2(+) stem/progenitor cells expand exclusively in SLG tumors. Lineage tracing experiments showed that SLG tumor cells undergo an extensive epithelial-mesenchymal transition (EMT) and TGF-beta-responding tumor cells are a source of mesenchymal tumor cells invading the surrounding stroma. This study advances our understanding of the mechanistic basis of salivary gland malignancy and may help combat this highly heterogeneous cancer.
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