pubmed.ncbi.nlm.nih.gov

The Contributions of Prostate Cancer Stem Cells in Prostate Cancer Initiation and Metastasis - PubMed

  • ️Tue Jan 01 2019

Review

The Contributions of Prostate Cancer Stem Cells in Prostate Cancer Initiation and Metastasis

Wenjuan Mei et al. Cancers (Basel). 2019.

Abstract

Research in the last decade has clearly revealed a critical role of prostate cancer stem cells (PCSCs) in prostate cancer (PC). Prostate stem cells (PSCs) reside in both basal and luminal layers, and are the target cells of oncogenic transformation, suggesting a role of PCSCs in PC initiation. Mutations in PTEN, TP53, and RB1 commonly occur in PC, particularly in metastasis and castration-resistant PC. The loss of PTEN together with Ras activation induces partial epithelial⁻mesenchymal transition (EMT), which is a major mechanism that confers plasticity to cancer stem cells (CSCs) and PCSCs, which contributes to metastasis. While PTEN inactivation leads to PC, it is not sufficient for metastasis, the loss of PTEN concurrently with the inactivation of both TP53 and RB1 empower lineage plasticity in PC cells, which substantially promotes PC metastasis and the conversion to PC adenocarcinoma to neuroendocrine PC (NEPC), demonstrating the essential function of TP53 and RB1 in the suppression of PCSCs. TP53 and RB1 suppress lineage plasticity through the inhibition of SOX2 expression. In this review, we will discuss the current evidence supporting a major role of PCSCs in PC initiation and metastasis, as well as the underlying mechanisms regulating PCSCs. These discussions will be developed along with the cancer stem cell (CSC) knowledge in other cancer types.

Keywords: metastasis; partial EMT; prostate cancer initiation; prostate cancer stem cells.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1

Review manuscript organization. (A) The typical prostate cancer (PC) pathogenesis involves tumor initiation, progression to metastatic diseases, and metastatic castration-resistant prostate cancers (mCRPCs) following androgen deprivation therapy (ADT) treatment. Prostate cancer stem cells (PCSCs) contribute to all these processes; this review will not cover the contributions of PCSCs to CRPC, but rather focus on the other two processes. PSC: prostate stem cells; CTCs: circulating tumor cells. (B) The mechanisms that regulate PCSC stemness will be discussed.

Figure 2
Figure 2

A dynamic model of cancer stem cells (CSCs). Intratumoral communications (black arrows with double directions) and tumor stromal communications (colored arrows with double directions) in (a) lead to the generation of CSCs (b). These communications will also drive CSC evolution (c).

Figure 3
Figure 3

Current evidence reveals a critical role of TP53 together with RB1 in the suppression of SOX2 expression and affecting other events (X). SOX2 and X confer the cell plasticity of PCSCs, which promotes PC metastasis and induces neuroendocrine PC (NEPC) in response to anti-androgen therapies.

Similar articles

Cited by

References

    1. Siegel R., Ward E., Brawley O., Jemal A. Cancer statistics, 2011: The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J. Clin. 2011;61:212–236. doi: 10.3322/caac.20121. - DOI - PubMed
    1. Shen M.M., Abate-Shen C. Molecular genetics of prostate cancer: New prospects for old challenges. Genes Dev. 2010;24:1967–2000. doi: 10.1101/gad.1965810. - DOI - PMC - PubMed
    1. Isaacs J.T., Coffey D.S. Etiology and disease process of benign prostatic hyperplasia. Prostate. Suppl. 1989;2:33–50. doi: 10.1002/pros.2990150506. - DOI - PubMed
    1. Lytton B. Prostate cancer: A brief history and the discovery of hormonal ablation treatment. J. Urol. 2001;165:1859–1862. doi: 10.1016/S0022-5347(05)66228-3. - DOI - PubMed
    1. Wong Y.N., Ferraldeschi R., Attard G., de Bono J. Evolution of androgen receptor targeted therapy for advanced prostate cancer. Nat. Rev. Clin. Oncol. 2014;11:365–376. doi: 10.1038/nrclinonc.2014.72. - DOI - PubMed

Publication types