Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomics.

Autor: Lu L; Department of Biochemistry and Molecular Genetics, and.; Center for Cancer Genomics, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA., Wang JR; Department of Head and Neck Surgery., Henderson YC; Department of Head and Neck Surgery., Bai S; Department of Genetics, and.; Department of Genitourinary Medical Oncology, University of Texas (UT) MD Anderson Cancer Center, Houston, Texas, USA., Yang J; Department of Radiation Oncology, New York University Langone School of Medicine, New York, New York, USA., Hu M; Department of Genetics, and., Shiau CK; Department of Biochemistry and Molecular Genetics, and.; Center for Cancer Genomics, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA., Pan T; The Driskill Graduate Program and., Yan Y; Department of Surgery, Northwestern University, Chicago, Illinois, USA., Tran TM; Department of Genetics, and., Li J; Department of Genetics, and., Kieser R; Center for RNA Therapeutics, Department of Cardiovascular Sciences, and.; Center for Bioinformatics and Computational Biology, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, Texas, USA., Zhao X; Department of Genetics, and., Wang J; Department of Head and Neck Surgery., Nurieva R; Department of Immunology., Williams MD; Department of Pathology, and., Cabanillas ME; Department of Endocrine Neoplasia and Hormonal Disorders, UT MD Anderson Cancer Center, Houston, Texas, USA., Dadu R; Department of Endocrine Neoplasia and Hormonal Disorders, UT MD Anderson Cancer Center, Houston, Texas, USA., Busaidy NL; Department of Endocrine Neoplasia and Hormonal Disorders, UT MD Anderson Cancer Center, Houston, Texas, USA., Zafereo M; Department of Head and Neck Surgery., Navin N; Department of Genetics, and.; Graduate School of Biological Sciences, University of Texas, Houston, Texas, USA.; Department of Bioinformatics and Computational Biology., Lai SY; Department of Head and Neck Surgery.; Graduate School of Biological Sciences, University of Texas, Houston, Texas, USA.; Department of Radiation Oncology, and.; Department of Molecular and Cellular Oncology, UT MD Anderson Cancer Center, Houston, Texas, USA., Gao R; Department of Biochemistry and Molecular Genetics, and.; Center for Cancer Genomics, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.; Department of Genetics, and.; The Driskill Graduate Program and.; Center for Bioinformatics and Computational Biology, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, Texas, USA.
Jazyk: angličtina
Zdroj: The Journal of clinical investigation [J Clin Invest] 2023 Jun 01; Vol. 133 (11). Date of Electronic Publication: 2023 Jun 01.
DOI: 10.1172/JCI169653
Abstrakt: The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC); however, the complex intratumor transformation process is poorly understood. We investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions using single-cell transcriptomic and genetic alteration data from patients with different subtypes of thyroid cancer. The resulting spectrum of ATC transformation included stress-responsive DTC cells, inflammatory ATC cells (iATCs), and mitotic-defective ATC cells and extended all the way to mesenchymal ATC cells (mATCs). Furthermore, our analysis identified 2 important milestones: (a) a diploid stage, in which iATC cells were diploids with inflammatory phenotypes and (b) an aneuploid stage, in which mATCs gained aneuploid genomes and mesenchymal phenotypes, producing excessive amounts of collagen and collagen-interacting receptors. In parallel, cancer-associated fibroblasts showed strong interactions among mesenchymal cell types, macrophages shifted from M1 to M2 states, and T cells reprogrammed from cytotoxic to exhausted states, highlighting new therapeutic opportunities for the treatment of ATC.
Databáze: MEDLINE