Immunohistochemical study of the neural development transcription factors (TTF1, ASCL1 and BRN2) in neuroendocrine prostate tumors

Rodríguez-Zarco, Enrique; Vallejo-Benítez, Ana; Umbría-Jiménez, Sebastián; Pereira-Gallardo, Sofia; Pabón-Carrasco, Sara; Azueta, Ainara; González‐Cámpora, Ricardo; Espinal, Paula S; García-Escudero, Antonio

doi:10.1016/j.acuroe.2017.07.007

Cited by 3 publications

(3 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NE cells present an epithelial phenotype. Next, in keeping with our aim to characterize NED, we sought to identify NE cells by evaluating the expression levels of 12 well-known NE markers that have been previously characterized as biomarker or driver genes of NEPC, such as ASCL1, CHGA/B, and FOXA2 24,28,29 . Using Seurat scoring strategy, we detected obvious NED in three patients (patient #2, #5, and #6; Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2020

View full text Add to dashboard Cite

Neuroendocrine 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.

show abstract

Section: Resultsmentioning

confidence: 99%

“…We used Seurat AddModuleScore function to evaluate the degrees to which individual cells express a certain pre-defined gene set as described previously 37,63 . For example, the NE gene set included ASCL1 28 (Fig. 1C).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Given that it is a master developmental regulator of neuronal cells, BRN2 appears to be a key modulator of invasion and metastasis in neuroendocrine‐type tumours and other tumours of neuronal origin. Notably, BRN2 has recently been reported to promote increased tumour aggressiveness in a subset of androgen receptor suppressed neuroendocrine prostate cancers (known as castration‐resistant prostate cancer (CRPC), a lethal subtype resistant to AR inhibitors such as enzalutamide) (Bishop et al., ) and has been suggested as a potential prognostic marker in small‐cell prostate carcinoma (Rodriguez‐Zarco et al., ). Interestingly, both NFIB and EZH2, two direct targets of BRN2 that drive invasion in melanoma (Fane et al., ), are also implicated in driving progression and metastasis of neuroendocrine tumours.…”

Section: Does Brn2 Modulate An Invasive Phenotype In Other Tumours?mentioning

confidence: 99%

BRN2, a POUerful driver of melanoma phenotype switching and metastasis

Fane

Chhabra

Smith

et al. 2018

Pigment Cell Melanoma Res

View full text Add to dashboard Cite

The POU domain family of transcription factors play a central role in embryogenesis and are highly expressed in neural crest cells and the developing brain. BRN2 is a class III POU domain protein that is a key mediator of neuroendocrine and melanocytic development and differentiation. While BRN2 is a central regulator in numerous developmental programs, it has also emerged as a major player in the biology of tumourigenesis. In melanoma, BRN2 has been implicated as one of the master regulators of the acquisition of invasive behaviour within the phenotype switching model of progression. As a mediator of melanoma cell phenotype switching, it coordinates the transition to a dedifferentiated, slow cycling and highly motile cell type. Its inverse expression relationship with MITF is believed to mediate tumour progression and metastasis within this model. Recent evidence has now outlined a potential epigenetic switching mechanism in melanoma cells driven by BRN2 expression that induces melanoma cell invasion. We summarize the role of BRN2 in tumour cell dissemination and metastasis in melanoma, while also examining it as a potential metastatic regulator in other tumour models.

show abstract

Neuroendocrine Differentiation of Prostate Cancer—An Intriguing Example of Tumor Evolution at Play

Patel

Chugh

Tripathi

2019

Cancers

View full text Add to dashboard Cite

Our understanding of neuroendocrine prostate cancer (NEPC) has assumed a new perspective in light of the recent advances in research. Although classical NEPC is rarely seen in the clinic, focal neuroendocrine trans-differentiation of prostate adenocarcinoma occurs in about 30% of advanced prostate cancer (PCa) cases, and represents a therapeutic challenge. Even though our knowledge of the mechanisms that mediate neuroendocrine differentiation (NED) is still evolving, the role of androgen deprivation therapy (ADT) as a key driver of this phenomenon is increasingly becoming evident. In this review, we discuss the molecular, cellular, and therapeutic mediators of NED, and emphasize the role of the tumor microenvironment (TME) in orchestrating the phenotype. Understanding the role of the TME in mediating NED could provide us with valuable insights into the plasticity associated with the phenotype, and reveal potential therapeutic targets against this aggressive form of PCa.

show abstract

Immunohistochemical study of the neural development transcription factors (TTF1, ASCL1 and BRN2) in neuroendocrine prostate tumors

Cited by 3 publications

References 14 publications

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

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

BRN2, a POUerful driver of melanoma phenotype switching and metastasis

Neuroendocrine Differentiation of Prostate Cancer—An Intriguing Example of Tumor Evolution at Play

Contact Info

Product

Resources

About