2. Academic Validation
  3. B4GALT1 Is a New Candidate to Maintain the Stemness of Lung Cancer Stem Cells

B4GALT1 Is a New Candidate to Maintain the Stemness of Lung Cancer Stem Cells

  • J Clin Med. 2019 Nov 9;8(11):1928. doi: 10.3390/jcm8111928.
Claudia De Vitis 1,  Giacomo Corleone 2,  Valentina Salvati 3,  Francesca Ascenzi 4,  Matteo Pallocca 2,  Francesca De Nicola 2,  Maurizio Fanciulli 2,  Simona di Martino 5,  Sara Bruschini 6,  Christian Napoli 7,  Alberto Ricci 8,  Massimiliano Bassi 9,  Federico Venuta 9,  Erino Angelo Rendina 10,  Gennaro Ciliberto 11,  Rita Mancini 1
Affiliations

Affiliations

  • 1 Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, "Sapienza" University of Rome, 00161 Rome, Italy.
  • 2 SAFU Laboratory, Department of Research, Advanced Diagnostic, and Technological Innovation, IRCCS "Regina Elena" National Cancer Institute, 00144 Rome, Italy.
  • 3 Preclinical Models and New Therapeutic Agents Unit, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy.
  • 4 Tumor Immunology and Immunotherapy Unit, Department of Research, Advanced Diagnostic and Technological Innovation, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.
  • 5 Pathology Unit, IRCSS "Regina Elena" National Cancer Institute, 00144 Rome, Italy.
  • 6 Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy.
  • 7 Department of Medical Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, "Sapienza" University of Rome, 00189 Rome, Italy.
  • 8 Department of Clinical and Molecular Medicine, Division of Pneumology, Sapienza University of Rome, Sant'Andrea Hospital, 00189 Rome, Italy.
  • 9 Department of Thoracic Surgery, University of Rome Sapienza, 00161 Rome, Italy.
  • 10 Department of Thoracic Surgery, Sant'Andrea Hospital, "Sapienza" University of Rome, 00189 Rome, Italy.
  • 11 Scientific Direction, IRCCS "Regina Elena" National Cancer Institute, 00144 Rome, Italy.
PMID: 31717588 DOI: 10.3390/jcm8111928
Abstract

Background: According to the Cancer Stem Cells (CSCs) hypothesis, a population of Cancer cells with stem cell properties is responsible for tumor propagation, drug resistance, and disease recurrence. Study of the mechanisms responsible for lung CSCs propagation is expected to provide better understanding of Cancer biology and new opportunities for therapy.

Methods: The Lung Adenocarcinoma (LUAD) NCI-H460 cell line was grown either as 2D or as 3D cultures. Transcriptomic and genome-wide chromatin accessibility studies of 2D vs. 3D cultures were carried out using RNA-sequencing and Assay for Transposase Accessible Chromatin with high-throughput Sequencing (ATAC-seq), respectively. Reverse transcription polymerase chain reaction (RT-PCR) was also carried out on RNA extracted from primary cultures derived from malignant pleural effusions to validate RNA-seq results.

Results: RNA-seq and ATAC-seq data disentangled transcriptional and genome accessibility variability of 3D vs. 2D cultures in NCI-H460 cells. The examination of genomic landscape of genes upregulated in 3D vs. 2D cultures led to the identification of 2D cultures led to the identification of Beta-1,4-galactosyltranferase 1 (B4GALT1) as the top candidate. B4GALT1 as the top candidate. B4GALT1 was validated as a stemness factor, since its silencing caused strong inhibition of 3D spheroid formation.

Conclusion: Combined transcriptomic and chromatin accessibility study of 3D vs. 2D LUAD cultures led to the identification of B4GALT1 as a new factor involved in the propagation and maintenance of LUAD CSCs.

Keywords

ATAC-seq; B4GALT1; CSCs; LUAD; NSCLC; RNA-seq; cancer stem cells; genome-wide; lung cancer; transcriptome.

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