@article{e4ab952318e94030a5babc552ae0f847,
title = "Single-cell RNA sequencing identifies a paracrine interaction that may drive oncogenic notch signaling in human adenoid cystic carcinoma",
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.",
keywords = "CP: Cancer, MYB, Notch1, adenoid cystic carcinoma, head and neck, luminal, myoepithelial, paracrine interaction, single cell sequencing",
author = "Parikh, {Anuraag S.} and Avishai Wizel and Daniel Davis and Armida Lefranc-Torres and Rodarte-Rascon, {Alejandro I.} and Miller, {Lauren E.} and Emerick, {Kevin S.} and Varvares, {Mark A.} and Deschler, {Daniel G.} and Faquin, {William C.} and Aster, {Jon C.} and Lin, {Derrick T.} and Bernstein, {Bradley E.} and Yotam Drier and Puram, {Sidharth V.}",
note = "Funding Information: This work was supported by the V Foundation (S.V.P.), Cancer Research Foundation (S.V.P.), Barnes-Jewish Hospital Foundation (S.V.P.), NCI K08CA237732 (S.V.P), NIDCR R21DE31072 (S.V.P.) NIDCR R21DE031366 (S.V.P.), the European Research Council Horizon 2020 grant 949029 (Y.D.), and the Adenoid Cystic Carcinoma Research Foundation (B.E.B. D.T.L. and J.C.A.). The funding sources had no involvement in the design, conduct, and reporting of the research. A.S.P. B.E.B. Y.D. and S.V.P. designed and executed the study and wrote and edited the manuscript. A.W. D.D. W.C.F. and J.C.A. performed data analysis and edited the manuscript. A.L.-T. A.I.R.-R. L.E.M. K.S.E. M.A.V. D.G.D. and D.T.L. provided patient samples and edited the manuscript. J.C.A. is a consultant to Ayala Pharmaceuticals, Remix Therapeutics, and Cellestia, Inc. B.E.B. declares outside interests in Fulcrum Therapeutics, Arsenal Biosciences, HiFiBio, Cell Signaling Technologies, and Chroma Medicine. Funding Information: This work was supported by the V Foundation (S.V.P.), Cancer Research Foundation (S.V.P.), Barnes-Jewish Hospital Foundation (S.V.P.), NCI K08CA237732 (S.V.P), NIDCR R21DE31072 (S.V.P.) NIDCR R21DE031366 (S.V.P.), the European Research Council Horizon 2020 grant 949029 (Y.D.), and the Adenoid Cystic Carcinoma Research Foundation (B.E.B., D.T.L., and J.C.A.). The funding sources had no involvement in the design, conduct, and reporting of the research. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = nov,
day = "29",
doi = "10.1016/j.celrep.2022.111743",
language = "English",
volume = "41",
journal = "Cell Reports",
issn = "2211-1247",
number = "9",
}