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Single-Cell RNA-seq Reveals a Subpopulation of Prostate Cancer Cells with Enhanced Cell-Cycle-Related Transcription and Attenuated Androgen Response.

Publication ,  Journal Article
Horning, AM; Wang, Y; Lin, C-K; Louie, AD; Jadhav, RR; Hung, C-N; Wang, C-M; Lin, C-L; Kirma, NB; Liss, MA; Kumar, AP; Sun, L; Liu, Z ...
Published in: Cancer Res
February 15, 2018

Increasing evidence suggests the presence of minor cell subpopulations in prostate cancer that are androgen independent and poised for selection as dominant clones after androgen deprivation therapy. In this study, we investigated this phenomenon by stratifying cell subpopulations based on transcriptome profiling of 144 single LNCaP prostate cancer cells treated or untreated with androgen after cell-cycle synchronization. Model-based clustering of 397 differentially expressed genes identified eight potential subpopulations of LNCaP cells, revealing a previously unappreciable level of cellular heterogeneity to androgen stimulation. One subpopulation displayed stem-like features with a slower cell doubling rate, increased sphere formation capability, and resistance to G2-M arrest induced by a mitosis inhibitor. Advanced growth of this subpopulation was associated with enhanced expression of 10 cell-cycle-related genes (CCNB2, DLGAP5, CENPF, CENPE, MKI67, PTTG1, CDC20, PLK1, HMMR, and CCNB1) and decreased dependence upon androgen receptor signaling. In silico analysis of RNA-seq data from The Cancer Genome Atlas further demonstrated that concordant upregulation of these genes was linked to recurrent prostate cancers. Analysis of receiver operating characteristic curves implicates aberrant expression of these genes and could be useful for early identification of tumors that subsequently develop biochemical recurrence. Moreover, this single-cell approach provides a better understanding of how prostate cancer cells respond heterogeneously to androgen deprivation therapies and reveals characteristics of subpopulations resistant to this treatment.Significance: Illustrating the challenge in treating cancers with targeted drugs, which by selecting for drug resistance can drive metastatic progression, this study characterized the plasticity and heterogeneity of prostate cancer cells with regard to androgen dependence, defining the character or minor subpopulations of androgen-independent cells that are poised for clonal selection after androgen-deprivation therapy. Cancer Res; 78(4); 853-64. ©2017 AACR.

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Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

February 15, 2018

Volume

78

Issue

4

Start / End Page

853 / 864

Location

United States

Related Subject Headings

  • RNA
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Male
  • Humans
  • Gene Expression Profiling
  • Cell Line, Tumor
  • Androgens
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Horning, A. M., Wang, Y., Lin, C.-K., Louie, A. D., Jadhav, R. R., Hung, C.-N., … Huang, T.-M. (2018). Single-Cell RNA-seq Reveals a Subpopulation of Prostate Cancer Cells with Enhanced Cell-Cycle-Related Transcription and Attenuated Androgen Response. Cancer Res, 78(4), 853–864. https://doi.org/10.1158/0008-5472.CAN-17-1924
Horning, Aaron M., Yao Wang, Che-Kuang Lin, Anna D. Louie, Rohit R. Jadhav, Chia-Nung Hung, Chiou-Miin Wang, et al. “Single-Cell RNA-seq Reveals a Subpopulation of Prostate Cancer Cells with Enhanced Cell-Cycle-Related Transcription and Attenuated Androgen Response.Cancer Res 78, no. 4 (February 15, 2018): 853–64. https://doi.org/10.1158/0008-5472.CAN-17-1924.
Horning AM, Wang Y, Lin C-K, Louie AD, Jadhav RR, Hung C-N, et al. Single-Cell RNA-seq Reveals a Subpopulation of Prostate Cancer Cells with Enhanced Cell-Cycle-Related Transcription and Attenuated Androgen Response. Cancer Res. 2018 Feb 15;78(4):853–64.
Horning, Aaron M., et al. “Single-Cell RNA-seq Reveals a Subpopulation of Prostate Cancer Cells with Enhanced Cell-Cycle-Related Transcription and Attenuated Androgen Response.Cancer Res, vol. 78, no. 4, Feb. 2018, pp. 853–64. Pubmed, doi:10.1158/0008-5472.CAN-17-1924.
Horning AM, Wang Y, Lin C-K, Louie AD, Jadhav RR, Hung C-N, Wang C-M, Lin C-L, Kirma NB, Liss MA, Kumar AP, Sun L, Liu Z, Chao W-T, Wang Q, Jin VX, Chen C-L, Huang TH-M. Single-Cell RNA-seq Reveals a Subpopulation of Prostate Cancer Cells with Enhanced Cell-Cycle-Related Transcription and Attenuated Androgen Response. Cancer Res. 2018 Feb 15;78(4):853–864.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

February 15, 2018

Volume

78

Issue

4

Start / End Page

853 / 864

Location

United States

Related Subject Headings

  • RNA
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Male
  • Humans
  • Gene Expression Profiling
  • Cell Line, Tumor
  • Androgens
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology