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

被引：80

作者：

Mei, Wenjuan ^{[1
,2
,3
,4
,5
]}

Lin, Xiaozeng ^{[2
,3
,4
,5
]}

Kapoor, Anil ^{[3
,4
,6
]}

Gu, Yan ^{[2
,3
,4
,5
]}

Zhao, Kuncheng ^{[2
,3
,4
,5
]}

Tang, Damu ^{[2
,3
,4
,5
]}

机构：

[1] Nanchang Univ, Dept Nephrol, Affiliated Hosp 1, Nanchang 330006, Jiangxi, Peoples R China

[2] McMaster Univ, Dept Med, Hamilton, ON L8S 4K1, Canada

[3] St Josephs Hosp, Res Inst St Joes Hamilton, Hamilton, ON L8N 4A6, Canada

[4] St Josephs Hosp, Hamilton Urol Oncol Res Ctr, Hamilton, ON L8N 4A6, Canada

[5] St Josephs Hosp, Hamilton Ctr Kidney Res, Hamilton, ON L8N 4A6, Canada

[6] McMaster Univ, Dept Surg, Hamilton, ON L8S 4K1, Canada

来源：

CANCERS | 2019年 / 11卷 / 04期

关键词：

prostate cancer stem cells; prostate cancer initiation; metastasis; partial EMT; CIRCULATING TUMOR-CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; MITOXANTRONE PLUS PREDNISONE; ACUTE MYELOID-LEUKEMIA; SIDE POPULATION CELLS; DNA-DAMAGE; ANDROGEN RECEPTOR; SELF-RENEWAL; LUMINAL CELLS; BASAL-CELLS;

D O I：

10.3390/cancers11040434

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：22