@article{2233cd2642144c55bfd618911fb6e51f,
title = "A mechanistic basis for the malignant progression of salivary gland tumors",
abstract = "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 HRASG12V-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-β-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.",
keywords = "Biological sciences, Cancer, Cell biology, Endocrinology",
author = "Sachiko Taniguchi and Yuya Tanaka and Ajit Elhance and Naoki Oshimori",
note = "Funding Information: We thank E. Fuchs for sharing the original LV vectors; L. Chin for TetO-Hras mice; F. Costantini for Rosa-YFP mice; D. Gadella for pmScarlet-i_C1 vector; We also thank D. Sauer for pathological assessment of mouse tumor tissues; OHSU's Department of Comparative Medicine (an AAALAC facility) for care and housing of our mouse colony. This work was supported by an NIH K99-R00 Pathway to Independence Award ( 4R00CA178197 ), an NIH R01 ( R01CA245535 ), and the start-up support from the Knight Cancer Institute/OHSU to N.O. Funding Information: We thank E. Fuchs for sharing the original LV vectors; L. Chin for TetO-Hras mice; F. Costantini for Rosa-YFP mice; D. Gadella for pmScarlet-i_C1 vector; We also thank D. Sauer for pathological assessment of mouse tumor tissues; OHSU's Department of Comparative Medicine (an AAALAC facility) for care and housing of our mouse colony. This work was supported by an NIH K99-R00 Pathway to Independence Award (4R00CA178197), an NIH R01 (R01CA245535), and the start-up support from the Knight Cancer Institute/OHSU to N.O. N.O. conceived and designed the study, supervised the experiments and analyses, prepared the figures, and wrote the manuscript. S.T. designed the study and performed the experiments, analyzed the data, prepared the figures, and participated in writing the manuscript. Y.T. performed the experiments and analyses. A.E. helped perform the experiments. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = dec,
day = "17",
doi = "10.1016/j.isci.2021.103508",
language = "English (US)",
volume = "24",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "12",
}