Single-cell RNA sequencing identifies a paracrine interaction that may drive oncogenic notch signaling in human adenoid cystic carcinoma

Anuraag S. Parikh, Avishai Wizel, Daniel Davis, Armida Lefranc-Torres, Alejandro I. Rodarte-Rascon, Lauren E. Miller, Kevin S. Emerick, Mark A. Varvares, Daniel G. Deschler, William C. Faquin, Jon C. Aster, Derrick T. Lin, Bradley E. Bernstein, Yotam Drier*, Sidharth V. Puram*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Salivary adenoid cystic carcinoma (ACC) is a rare, biologically unique biphasic tumor that consists of malignant myoepithelial and luminal cells. MYB and Notch signaling have been implicated in ACC pathophysiology, but in vivo descriptions of these two programs in human tumors and investigation into their active coordination remain incomplete. We utilize single-cell RNA sequencing to profile human head and neck ACC, including a comparison of primary ACC with a matched local recurrence. We define expression heterogeneity in these rare tumors, uncovering diversity in myoepithelial and luminal cell expression. We find differential expression of Notch ligands DLL1, JAG1, and JAG2 in myoepithelial cells, suggesting a paracrine interaction that may support oncogenic Notch signaling. We validate this selective expression in three published cohorts of patients with ACC. Our data provide a potential explanation for the biphasic nature of low- and intermediate-grade ACC and may help direct new therapeutic strategies against these tumors.

Original languageAmerican English
Article number111743
JournalCell Reports
Volume41
Issue number9
DOIs
StatePublished - 29 Nov 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors

Keywords

  • CP: Cancer
  • MYB
  • Notch1
  • adenoid cystic carcinoma
  • head and neck
  • luminal
  • myoepithelial
  • paracrine interaction
  • single cell sequencing

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