Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

The spectrum of neuroendocrine differentiation in prostate cancer

Prostate Cancer and Prostatic Diseases volume 24, pages 1214–1215 (2021)Cite this article

Subjects

The Original Article was published on 20 April 2020

In the accompanying PCAN-21-0170 Letter, Yang et al. commented on our previous report that YAP1 expression is increased in advanced adenocarcinomas (AdPCa) but decreased in neuroendocrine prostate cancer (NEPC) [1]. Their comments are summarized below in three main points and addressed accordingly:

  1. 1.

    About cell lines. Yang et al. write, “PC3 should also be considered as an NEPC cell line” and “we recommend the authors take further explore at the other NEPC cell lines to provide more evidences, like the LASCPC-01.”

    Although PC3 cells express certain NEPC genes, they are not full blown NEPC. Because of this, PC3 and their derivatives can be induced to undergo NE differentiation by radiation, activation of CXCL12γ or CREB, reduced TSP1 or ATF2, or agents such as epidrug, cAMP and Dovitinib [2,3,4,5]. The expression of certain NE genes in PC3 suggests a transitional state. Our research [1] provides evidence strengthening this concept, and our data suggest that YAP1 might be a key molecule that controls the progression from AdPCa to NEPC (Fig. 1).

    Fig. 1: NE features of PCa cell lines.
    figure 1

    (A) Heatmap of 20 NEPC-related genes. Gene expression data were extracted from RNASeq collected by CCLE. (B) The spectrum and key events of NE differentiation in PCa.

    Full size image

    As for the LASCPC-01 cell line that we did not include in our paper, we analyzed only PCa cell lines that have available RNAseq data collected by CCLE, which does not include LASCPC-01. The exclusion of the LASCPC-1 from our research has little or no impact upon the veracity of our findings.

    With regards to the issues raised about cell lines, we believe that those well versed in the relevant literature on PCa cell lines will take no issue with our usage of PC3 or exclusion of LASCPC-01 nor contest our findings on these specific grounds.

  2. 2.

    About the YAP1/AR axis in NEPC. Yang et al. write, “this pathway may play the role in AR expression rather than NED” and “we recommend the authors should focus on the YAP1 and AR, instead of NED.”

    This is part of a future direction of my team’s work and an extension of the findings of this paper [1]. Now that we have established the loss of YAP1 in NEPC, we are exploring the role of the YAP1/Wnt/AR axis in PCa.

  3. 3.

    About increased YAP1 expression in advanced adenocarcinomas where NE markers may also be elevated. Yang et al think “If the YAP1 lost related to NEPC as authors proposed, the NE markers should decline”.

About cell lines. Yang et al. write, “PC3 should also be considered as an NEPC cell line” and “we recommend the authors take further explore at the other NEPC cell lines to provide more evidences, like the LASCPC-01.”

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: NE features of PCa cell lines.

References

  1. Cheng S, Prieto-Dominguez N, Yang S, Connelly ZM, StPierre S, Rushing B, et al. The expression of YAP1 is increased in high-grade prostatic adenocarcinoma but is reduced in neuroendocrine prostate cancer. Prostate Cancer Prostatic Dis. 2020;23:661–9.

  2. Bang YJ, Pirnia F, Fang WG, Kang WK, Sartor O, Whitesell L, et al. Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP. Proc Natl Acad Sci. 1994;91:5330–4.

    Article  CAS  Google Scholar 

  3. Yadav SS, Li J, Stockert JA, Herzog B, O’Connor J, Garzon-Manco L, et al. Induction of neuroendocrine differentiation in prostate cancer cells by dovitinib (TKI-258) and its therapeutic implications. Transl Oncol. 2017;10:357–66.

    Article  Google Scholar 

  4. Jung Y, Cackowski FC, Yumoto K, Decker AM, Wang J, Kim JK, et al. CXCL12γ promotes metastatic castration-resistant prostate cancer by inducing cancer stem cell and neuroendocrine phenotypes. Cancer Res. 2018;78:2026–39.

    Article  CAS  Google Scholar 

  5. Lee E, Wang J, Jung Y, Cackowski FC, Taichman RS. Reduction of two histone marks, H3k9me3 and H3k27me3 by epidrug induces neuroendocrine differentiation in prostate cancer. J Cell Biochem. 2018;119:3697–705.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research is supported by NIH R01 CA226285 grant to YX.

Author information

Authors and Affiliations

  1. Department of Biochemistry & Molecular Biology, LSU Health Shreveport, Shreveport, LA, USA

    Siyuan Cheng & Xiuping Yu

Authors
  1. Siyuan Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiuping Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiuping Yu.

Ethics declarations

Conflict of interest

The authors declare no competing interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cheng, S., Yu, X. The spectrum of neuroendocrine differentiation in prostate cancer. Prostate Cancer Prostatic Dis 24, 1214–1215 (2021). https://doi.org/10.1038/s41391-021-00386-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41391-021-00386-5

Search

Advanced search

Quick links