scholarly journals Single-cell analysis supports a luminal-neuroendocrine trans-differentiation in human prostate cancer

2020 ◽  
Author(s):  
Baijun Dong ◽  
Juju Miao ◽  
Yanqing Wang ◽  
Wenqin Luo ◽  
Zhongzhong Ji ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
Single Cell Analysis ◽  
Neuroendocrine Differentiation ◽  
Neuroendocrine Cells ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Neuroendocrine Prostate Cancer ◽  
Neuroendocrine Transdifferentiation

AbstractNeuroendocrine prostate cancer is one of the most aggressive subtypes of prostate tumor. Although much progress has been made in understanding the development of neuroendocrine prostate cancer, the cellular architecture associated with neuroendocrine differentiation in human prostate cancer remain incompletely understood. Here, we use single-cell RNA sequencing to profile the transcriptomes of 21,292 cells from needle biopsies of 6 castration-resistant prostate cancers. Our analyses reveal that all neuroendocrine tumor cells display a luminal-like epithelial phenotype. In particular, lineage trajectory analysis suggests that focal neuroendocrine differentiation exclusively originate from luminal-like malignant cells rather than basal compartment. Further tissue microarray analysis validates the generality of the luminal phenotype of neuroendocrine cells. Moreover, we uncover neuroendocrine differentiation-associated gene signatures that may help us to further explore novel intrinsic molecular mechanisms deriving neuroendocrine prostate cancer. In summary, our single-cell study provides direct evidence into the cellular states underlying neuroendocrine transdifferentiation in human prostate cancer.

scholarly journals Single-cell analysis supports a luminal-neuroendocrine transdifferentiation in human prostate cancer

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Baijun Dong ◽  
Juju Miao ◽  
Yanqing Wang ◽  
Wenqin Luo ◽  
Zhongzhong Ji ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
Single Cell Analysis ◽  
Neuroendocrine Differentiation ◽  
Neuroendocrine Cells ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Neuroendocrine Prostate Cancer ◽  
Neuroendocrine Transdifferentiation

AbstractNeuroendocrine prostate cancer is one of the most aggressive subtypes of prostate tumor. Although much progress has been made in understanding the development of neuroendocrine prostate cancer, the cellular architecture associated with neuroendocrine differentiation in human prostate cancer remain incompletely understood. Here, we use single-cell RNA sequencing to profile the transcriptomes of 21,292 cells from needle biopsies of 6 castration-resistant prostate cancers. Our analyses reveal that all neuroendocrine tumor cells display a luminal-like epithelial phenotype. In particular, lineage trajectory analysis suggests that focal neuroendocrine differentiation exclusively originate from luminal-like malignant cells rather than basal compartment. Further tissue microarray analysis validates the generality of the luminal phenotype of neuroendocrine cells. Moreover, we uncover neuroendocrine differentiation-associated gene signatures that may help us to further explore other intrinsic molecular mechanisms deriving neuroendocrine prostate cancer. In summary, our single-cell study provides direct evidence into the cellular states underlying neuroendocrine transdifferentiation in human prostate cancer.

scholarly journals Overexpression of an α1H(Cav3.2) T-type Calcium Channel during Neuroendocrine Differentiation of Human Prostate Cancer Cells

2002 ◽  
Vol 277 (13) ◽  
pp. 10824-10833 ◽  
Author(s):  
Pascal Mariot ◽  
Karine Vanoverberghe ◽  
Nathalie Lalevée ◽  
Michel F. Rossier ◽  
Natalia Prevarskaya
Keyword(s):  
Prostate Cancer ◽  
Calcium Channel ◽  
Cancer Cells ◽  
Neuroendocrine Differentiation ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells

Characterization of CD133+/CD44+ human prostate cancer stem cells with ATR-FTIR spectroscopy

The Analyst ◽  
2019 ◽  
Vol 144 (6) ◽  
pp. 2138-2149 ◽  
Author(s):  
Günnur Güler ◽  
Ummu Guven ◽  
Gulperi Oktem
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Ftir Spectroscopy ◽  
Molecular Mechanisms ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Stem Cells

Molecular mechanisms and features of prostate cancer stem cells, which are crucial for improving target specific therapies, were elucidated with ATR-FTIR spectroscopy.

NeuroD1 Expression in Human Prostate Cancer: Can It Contribute to Neuroendocrine Differentiation Comprehension?

2007 ◽  
Vol 52 (5) ◽  
pp. 1365-1373 ◽  
Author(s):  
Luca Cindolo ◽  
Renato Franco ◽  
Monica Cantile ◽  
Giulia Schiavo ◽  
Giuseppina Liguori ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Neuroendocrine Differentiation ◽  
Human Prostate ◽  
Human Prostate Cancer

scholarly journals TRIM59 is Suppressed by Androgen Receptor and Acts to Promote Lineage Plasticity and Neuroendocrine Differentiation in Prostate Cancer

2021 ◽  
Author(s):  
Liancheng Fan ◽  
Yiming Gong ◽  
Yuman He ◽  
Wei-Qiang Gao ◽  
Baijun Dong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Molecular Mechanisms ◽  
Neuroendocrine Differentiation ◽  
Tumor Model ◽  
Strongly Correlated ◽  
Neuroendocrine Prostate Cancer ◽  
In Vitro Effects

Abstract Background: The incidence of treatment-induced neuroendocrine prostate cancer (t-NEPC) has been greatly increasing after the usage of second-generation androgen receptor (AR) pathway inhibitors (ARPIs). Neuroendocrine differentiation (NED) is closely associated with ARPI treatment failure and poor prognosis in prostate cancer (PCa) patients. However, the molecular mechanisms of NED are not fully understood. Methods: TRIM59 expression was evaluated in PCa samples from patients at first diagnosis or at relapse stage post ARPI treatment by immunohistochemistry; in vitro effects of TRIM59 were determined by cell proliferation, sphere formation and cell migration assays; while in vivo analysis was performed using subcutaneous tumor model. Western blot, qPCR assay, dual luciferase assessment, chromatin immunoprecipitation and RNA sequencing were applied for mechanistic exploration.Results: Here we report that upregulation of TRIM59, a TRIM family protein, is strongly correlated with ARPI treatment mediated NED and shorter patient survival in PCas. AR binds to TRIM59 promoter and represses its transcription. ARPI treatment leads to a reversal of repressive epigenetic modifications on TRIM59 gene and the transcriptional restraint on TRIM59 by AR. Upregulated TRIM59 then drives the NED of PCa by enhancing the degradation of RB1 and P53 and upregulating downstream lineage plasticity-promoting transcription factor SOX2. Conclusion: Altogether, TRIM59 is negatively regulated by AR and acts as a key driver for NED in PCas. Our study provides a novel prognostic marker for PCas and shed new light on the molecular pathogenesis of t-NEPC, a deadly variant of PCa.

scholarly journals Human Prostate Cancer-Associated Macrophage Subtypes with Prognostic Potential Revealed by Single-cell Transcriptomics

2020 ◽  
Author(s):  
Joseph C Siefert ◽  
Bianca Cioni ◽  
Mauro J Muraro ◽  
Mohammed Alshalalfa ◽  
Judith Vivié ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Single Cell ◽  
Cancer Progression ◽  
Human Tumor ◽  
Tumour Microenvironment ◽  
Gene Signature ◽  
Human Prostate ◽  
M2 Macrophage ◽  
Human Prostate Cancer ◽  
Macrophage Subtypes

ABSTRACTMacrophages in the tumor microenvironment are causally linked with prostate cancer development and progression, yet little is known about their composition in neoplastic human tissue. By performing single cell transcriptomic analysis of human prostate cancer resident macrophages, three distinct populations were identified in the diseased prostate. Unexpectedly, macrophages isolated from the tumor-adjacent site of the prostatectomy specimen were identical to those from the tumorous site. Markers associated with canonical M1 and M2 macrophage phenotypes were identifiable, however these were not the main factors defining unique subtypes. The genes selectively associated with each macrophage cluster were used to develop a gene signature which was highly associated with both recurrence-free and metastasis-free survival. These results highlight the relevance of tissue-specific macrophage subtypes in the tumour microenvironment for prostate cancer progression and demonstrates the utility of profiling single-cell transcriptomics in human tumor samples as a strategy to design gene classifiers for patient prognostication.

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