A mechanistic basis for the malignant progression of salivary gland tumors

Sachiko Taniguchi; Yuya Tanaka; Ajit Elhance; Naoki Oshimori

doi:10.1016/j.isci.2021.103508

A mechanistic basis for the malignant progression of salivary gland tumors

iScience. 2021 Nov 25;24(12):103508. doi: 10.1016/j.isci.2021.103508. eCollection 2021 Dec 17.

Authors

Sachiko Taniguchi¹, Yuya Tanaka¹, Ajit Elhance¹, Naoki Oshimori^{1

2

3

4}

Affiliations

¹ Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA.
² Department of Dermatology, Oregon Health and Science University, Portland, OR 97239, USA.
³ Department of Otolaryngology, Head & Neck Surgery, Oregon Health and Science University, Portland, OR 97239, USA.
⁴ Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.

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 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-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.

Abstract

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