Subtype Transdifferentiation in Human Cancer: The Power of Tissue Plasticity in Tumor Progression DOI Creative Commons
Monica Fedele, Laura Cerchia, Sabrina Battista

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(4), P. 350 - 350

Published: Feb. 17, 2024

The classification of tumors into subtypes, characterized by phenotypes determined specific differentiation pathways, aids diagnosis and directs therapy towards targeted approaches. However, with the advent explosion next-generation sequencing, cancer are turning out to be far more heterogenous than initially thought, is continually being updated include subtypes. Tumors indeed highly dynamic, they can evolve undergo various changes in their characteristics during disease progression. picture becomes even complex when tumor responds a therapy. In all these cases, cells acquire ability transdifferentiate, changing subtype, adapt microenvironments. These modifications affect tumor’s growth rate, invasiveness, response treatment, overall clinical behavior. Studying subtype transitions crucial for understanding evolution, predicting outcomes, developing personalized treatment strategies. We discuss this emerging hallmark molecular mechanisms involved at crossroads between microenvironment, focusing on four different human cancers which tissue plasticity causes switch: breast cancer, prostate glioblastoma, pancreatic adenocarcinoma.

Language: Английский

Complexities of Prostate Cancer DOI Open Access
Sobia Wasim, Sang‐Yoon Lee, Jaehong Kim

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 14257 - 14257

Published: Nov. 17, 2022

Prostate cancer has a long disease history and wide variety uncertainty in individual patients’ clinical progress. In recent years, we have seen revolutionary advance both prostate patient care the research field. The power of deep sequencing provided cistromic transcriptomic knowledge that not discovered before. Our understanding biology, from bedside molecular imaging techniques, also been greatly advanced. It is important our current theragnostic schemes, including diagnostic modalities, therapeutic responses, drugs available to target non-AR signaling should be improved. This review article discusses progress biology advances strategies.

Language: Английский

Citations

86
The implications of single-cell RNA-seq analysis in prostate cancer: unraveling tumor heterogeneity, therapeutic implications and pathways towards personalized therapy DOI Creative Commons
Dechao Feng,

Weizhen Zhu,

Jie Wang

et al.

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: April 11, 2024

Abstract In recent years, advancements in single-cell and spatial transcriptomics, which are highly regarded developments the current era, particularly emerging integration of spatiotemporal have enabled a detailed molecular comprehension complex regulation cell fate. The insights obtained from these methodologies anticipated to significantly contribute development personalized medicine. Currently, technology is less frequently utilized for prostate cancer compared with other types tumors. Starting perspective RNA sequencing technology, this review outlined significance (scRNA-seq) research, encompassing preclinical medicine clinical applications. We summarize differences between mouse human as revealed by scRNA-seq studies, well combination multi-omics methods involving highlight key targets diagnosis, treatment, drug resistance characteristics cancer. These studies expected provide novel immunotherapy innovative treatment strategies castration-resistant Furthermore, we explore potential applications stemming technologies review, paving way future research precision

Language: Английский

Citations

26
Molecular panorama of therapy resistance in prostate cancer: a pre-clinical and bioinformatics analysis for clinical translation DOI
Milad Ashrafizadeh, Wei Zhang, Yu Tian

et al.

Cancer and Metastasis Reviews, Journal Year: 2024, Volume and Issue: 43(1), P. 229 - 260

Published: Feb. 19, 2024

Language: Английский

Citations

17
Zeb1-controlled metabolic plasticity enables remodeling of chromatin accessibility in the development of neuroendocrine prostate cancer DOI
Deng Wang,

Genyu Du,

Xinyu Chen

et al.

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: 31(6), P. 779 - 791

Published: April 23, 2024

Language: Английский

Citations

17
Spatial Gene Expression Analysis Reveals Characteristic Gene Expression Patterns of De Novo Neuroendocrine Prostate Cancer Coexisting with Androgen Receptor Pathway Prostate Cancer DOI Open Access
Ryuta Watanabe, Noriyoshi Miura, Mie Kurata

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8955 - 8955

Published: May 18, 2023

Neuroendocrine prostate carcinoma (NEPC) accounts for less than 1% of neoplasms and has extremely poorer prognosis the typical androgen receptor pathway-positive adenocarcinoma (ARPC). However, very few cases in which de novo NEPC APRC are diagnosed simultaneously same tissue have been reported. We report herein a 78-year-old man metastatic coexisting with ARPC treated at Ehime University Hospital. Visium CytAssist Spatial Gene Expression analysis (10× genetics) was performed using formalin-fixed, paraffin-embedded (FFPE) samples. The neuroendocrine signatures were upregulated sites, sites. TP53, RB1, or PTEN upregulation homologous recombination repair genes sites not downregulated. Urothelial markers elevated. Meanwhile, Rbfox3 SFRTM2 levels downregulated while fibrosis HGF, HMOX1, ELN, GREM1 tumor microenvironment NEPC. In conclusion, findings spatial gene expression patient accumulation basic data will help development novel treatments improve patients castration-resistant cancer.

Language: Английский

Citations

27
Integrated analysis of single-cell and bulk transcriptomics develops a robust neuroendocrine cell-intrinsic signature to predict prostate cancer progression DOI Creative Commons
Tingting Zhang, Faming Zhao,

Yahang Lin

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(3), P. 1065 - 1080

Published: Jan. 1, 2024

Neuroendocrine prostate cancer (NEPC) typically implies severe lethality and limited treatment options.The precise identification of NEPC cells holds paramount significance for both research clinical applications, yet valid biomarker remains to be defined.Methods: Leveraging 11 published NE-related gene sets, single-cell RNA-sequencing (scRNA-seq) cohorts, 15 bulk transcriptomic 13 experimental models (PCa), we employed multiple advanced algorithms construct validate a robust risk prediction model.Results: Through the compilation comprehensive scRNA-seq reference atlas (comprising total 210,879 single cells, including 66 tumor samples) from 9 multicenter datasets PCa, observed inconsistent inefficient performance among NE sets.Therefore, developed an integrative analysis pipeline, identifying 762 high-quality markers.Subsequently, derived cell-intrinsic signature, R package named NEPAL, predict scores.By applying independent validation datasets, NEPAL consistently accurately assigned feature delineated PCa progression.Intriguingly, demonstrated predictive capabilities prognosis therapy responsiveness, as well potential epigenetic drivers NEPC. Conclusion:The present study furnishes valuable tool monitoring progression through profiles obtained sources.

Language: Английский

Citations

13
CDK12 regulates angiogenesis of advanced prostate cancer by IGFBP3 DOI Creative Commons

Kun Zhong,

Wenwu Luo, Nan Li

et al.

International Journal of Oncology, Journal Year: 2024, Volume and Issue: 64(2)

Published: Jan. 4, 2024

Prostate cancer (PCa) is a prevalent malignancy among men, with majority of patients presenting distant metastases at the time initial diagnosis. These are heightened risk developing more aggressive castration‑resistant PCa following androgen deprivation therapy, which poses greater challenge for treatment. Notably, inhibition tumor angiogenesis should not be considered an ineffective treatment strategy. The regulatory role CDK12 in transcriptional and post‑transcriptional processes essential proper functioning various cellular processes. In present study, expression was first knocked down cells using CRISPR or siRNA technology. Subsequently, RNA‑seq analysis, co‑immunoprecipitation, western blotting, reverse transcription‑quantitative polymerase chain reaction LinkedOmics database were employed to reveal that inhibits insulin like growth factor binding protein 3 (IGFBP3). Western blot analysis also demonstrated promoted VEGFA by inhibiting IGFBP3, involves Akt signaling pathway. Then, found promote cell proliferation, migration IGFBP3 through proliferation assays, assays tube formation respectively. Finally, animal experiments performed in vivo validation. It concluded its IGFBP3.

Language: Английский

Citations

7
Role of transcription factors and chromatin modifiers in driving lineage reprogramming in treatment-induced neuroendocrine prostate cancer DOI Creative Commons

Amritha Sreekumar,

Sharanjot Saini

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Jan. 12, 2023

Therapy-induced neuroendocrine prostate cancer (NEPC) is a highly lethal variant of that increasing in incidence with the increased use next-generation androgen receptor (AR) pathway inhibitors. It arises via reversible trans-differentiation process, referred to as differentiation (NED), wherein cells show decreased expression AR and (NE) lineage markers including enolase 2 (ENO2), chromogranin A (CHGA) synaptophysin (SYP). NEPC associated poor survival rates these tumors are aggressive often metastasize soft tissues such liver, lung central nervous system despite low serum PSA levels relative disease burden. has been recognized therapy-induced NED involves series genetic epigenetic alterations act concerted manner orchestrating switching. In recent years, we have seen spurt research this area implicated host transcription factors modifiers play role driving article, review important chromatin instrumental reprogramming adenocarcinomas under selective pressure various AR-targeted therapies. With an understanding temporal spatial interplay their gene programs NEPC, better therapeutic strategies being tested for targeting effectively.

Language: Английский

Citations

13
Defined cellular reprogramming of androgen receptor-active prostate cancer to neuroendocrine prostate cancer DOI Creative Commons
Shan Li, Kai Song,

Huiyun Sun

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

SUMMARY Neuroendocrine prostate cancer (NEPC) arises primarily through neuroendocrine transdifferentiation (NEtD) as an adaptive mechanism of therapeutic resistance. Models to define the functional effects putative drivers this process on androgen receptor (AR) signaling and NE lineage programs are lacking. We adapted a genetically defined strategy from field cellular reprogramming directly convert AR-active (ARPC) AR-independent NEPC using candidate factors. delineated critical roles pioneer factors ASCL1 NeuroD1 in NEtD uncovered their abilities silence AR expression by remodeling chromatin at somatically acquired enhancer global binding sites with activity. also elucidated dynamic temporal changes transcriptomic epigenomic landscapes cells undergoing acute conversion ARPC which should inform future development. Further, we distinguished activities inactivation RE-1 silencing transcription factor (REST), master suppressor major neuronal gene program, establishing state modulating genes associated histocompatibility complex class I (MHC I) antigen processing presentation. These findings provide important, clinically relevant insights into biological processes driving cancer.

Language: Английский

Citations

0
New insights into markers for distinguishing neuroendocrine prostate cancer: evidence from single-cell analysis DOI Creative Commons

Hailang Luo,

Boyang Li, Meng Zhang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 14, 2025

Neuroendocrine prostate cancer (NEPC) is a highly aggressive malignancy with few effective treatment options. The identification of reliable biomarkers for NEPC essential early detection and intervention. We combined single-cell bulk transcriptome analysis to identify novel markers NEPC. InferCNV assess copy number variations leveraging consensus non-negative matrix factorization (cNMF) characterize transcriptional programs. Pseudotime was used decipher (PCa) progression differentiation trajectory. BayesPrism integrates results TCGA-PRAD sequencing information further study prognostic features. Immunohistochemistry (IHC) performed validate the elevated expression ASCL1 WDFY4 in identified five distinct programs PCa malignant epithelial cells, where Module 3 presented patterns, activation DNA replication cell cycle pathways classical marker expression. Patients high proportion correlated poor clinical outcomes, advanced Gleason scores, higher T stages. highlighted key trajectory-dependent genes involved transition NEPC, progressing fate, which were confirmed by IHC analysis, indicating that might be potential distinguishing Combined we highlight cellular heterogeneity programs, validated Providing foundation prediction management.

Language: Английский

Citations

0