Video tracking of single cells to identify clustering behavior DOI Creative Commons
Mónica Suárez Korsnes, Håkon Ramberg, Kristin Austlid Taskén

et al.

Frontiers in Imaging, Journal Year: 2024, Volume and Issue: 3

Published: Dec. 2, 2024

Cancer cell clustering is a critical factor in metastasis, with cells often believed to migrate groups as they establish themselves new environments. This study presents preliminary findings from an vitro experiment, suggesting that co-culturing provides effective method for observing this phenomenon, even though the are grown monolayers. We introduce novel single-cell tracking approach based on graph theory identify clusters PC3 cultivated both monoculture and co-culture PC12 cells, using 66-h time-lapse recordings. The initial step consists of defining “linked” pairs laying foundation application theory. propose two alternative definitions pairings. first method, Method 1 , defines at given time t if close together within defined period before after . A second potential 2 there overlap between convex hulls their respective tracks during period. Pairing enables subsequent analysis. framework represents vertex (node) relation edge. An interconnected set high-degree nodes (nodes many connections or edges) forms subgraph, backbone, patch (cluster) cells. All connected backbone part subgraph. functions partition (or cut) graph. Two consecutive video considered share same identity following cluster contains least p = 75 % preceding cluster, mean positions △ r 75μm. appear form persistent exceeding 10 40–50 h incubation seeding. In contrast, cultured alone (mono-culture) did not exhibit behavior. experimental requires further validation broader dataset.

Language: Английский

Killing SCLC: insights into how to target a shapeshifting tumor DOI Open Access
Kate D. Sutherland, Abbie S. Ireland, Trudy G. Oliver

et al.

Genes & Development, Journal Year: 2022, Volume and Issue: 36(5-6), P. 241 - 258

Published: March 1, 2022

Small cell lung cancer (SCLC) is a rapidly growing, highly metastatic, and relatively immune-cold subtype. Historically viewed in the laboratory clinic as single disease, new discoveries suggest that SCLC comprises multiple molecular subsets. Expression of MYC family members lineage-related transcription factors ASCL1, NEUROD1, POU2F3 (and, some studies, YAP1) define unique states have been associated with distinct responses to variety therapies. However, tumors exhibit high degree intratumoral heterogeneity, recent studies suggesting existence tumor plasticity phenotypic switching between subtype states. While correlated with, likely drives, therapeutic resistance, mechanisms underlying this are still largely unknown. Subtype also immune-related gene expression, which impacts response immune checkpoint blockade may reveal novel targets for alternative immunotherapeutic approaches. In review, we synthesize on how these processes impinge antitumor immunity.

Language: Английский

Citations

52
Calcium signalling pathways in prostate cancer initiation and progression DOI
Roberto Silvestri, Vanessa Nicolì, Priyadarsini Gangadharannambiar

et al.

Nature Reviews Urology, Journal Year: 2023, Volume and Issue: 20(9), P. 524 - 543

Published: March 24, 2023

Language: Английский

Citations

26
A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1 DOI Creative Commons
Shuai Yuan,

Shaohua He,

Luyao Li

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 6, 2023

Abstract SLC12A5, a neuron-specific potassium-chloride co-transporter, has been reported to promote tumor progression, however, the underlying mechanism remains unclear. Here we report that SLC12A5 functions as an oncogene progression and castration resistance of prostate cancer through N6-methyladenosine (m 6 A) reader YTHDC1 transcription factor HOXB13. We have shown level was increased in cancer, comparison its normal counterparts, further elevated castration-resistant (CRPC). The enhanced expression mRNA associated with neuroendocrine (NEPC) poor survival cancer. Furthermore, demonstrated promoted development addition cell proliferation migration. Interestingly, detected nucleus formed complex nuclear m A YTHDC1, which turn upregulated HOXB13 progression. Therefore, our findings reveal how cotransporter promotes provide therapeutic opportunity for apply neurological disorder drug inhibitors.

Language: Английский

Citations

21
DPYSL5 is highly expressed in treatment-induced neuroendocrine prostate cancer and promotes lineage plasticity via EZH2/PRC2 DOI Creative Commons
Roosa Kaarijärvi, Heidi Kaljunen, Lucia Nappi

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Jan. 18, 2024

Abstract Treatment-induced neuroendocrine prostate cancer (t-NEPC) is a lethal subtype of castration-resistant resistant to androgen receptor (AR) inhibitors. Our study unveils that AR suppresses the neuronal development protein dihydropyrimidinase-related 5 (DPYSL5), providing mechanism for transformation under deprivation therapy. unique CRPC-NEPC cohort, comprising 135 patient tumor samples, including 55 t-NEPC exhibits high expression DPYSL5 in tumors. correlates with neuroendocrine-related markers and inversely PSA. overexpression cells induces neuron-like phenotype, enhances invasion, proliferation, upregulates stemness markers. Mechanistically, promotes cell plasticity via EZH2-mediated PRC2 activation. Depletion decreases G1 phase cycle arrest, reverses luminal genes. In conclusion, plays critical role regulating plasticity, we propose AR/DPYSL5/EZH2/PRC2 axis as driver progression.

Language: Английский

Citations

6
The Role of Perineural Invasion in Prostate Cancer and Its Prognostic Significance DOI Open Access

Yuequn Niu,

Sarah Förster, Michael H. Muders

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(17), P. 4065 - 4065

Published: Aug. 23, 2022

Perineural invasion (PNI) is a common indication of tumor metastasis that can be detected in multiple malignancies, including prostate cancer. In the development PNI, cells closely interact with nerve components microenvironment and create perineural niche, which provides supportive surrounding for their survival benefits cells. Various transcription factors, cytokines, chemokines, related signaling pathways have been reported to important progress PNI. Nevertheless, current understanding molecular mechanism PNI still very limited. Clinically, commonly associated adverse clinicopathological parameters poor outcomes cancer patients. However, whether could act as an independent prognostic predictor remains controversial among studies due inconsistent research aim endpoint, sample type, statistical methods, and, most importantly, definition inclusion criteria. this review, we provide summary comparison significance based on existing literature propose more standardized description would helpful better its clinical relevance.

Language: Английский

Citations

25
Androgen deprivation induces neuroendocrine phenotypes in prostate cancer cells through CREB1/EZH2-mediated downregulation of REST DOI Creative Commons
Dayong Zheng, Yan Zhang, Sukjin Yang

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: May 22, 2024

Abstract Although effective initially, prolonged androgen deprivation therapy (ADT) promotes neuroendocrine differentiation (NED) and prostate cancer (PCa) progression. It is incompletely understood how ADT transcriptionally induces NE genes in PCa cells. CREB1 REST are known to positively negatively regulate neuronal gene expression the brain, respectively. No direct link between these two master regulators has been elucidated NED of PCa. We show that mRNA downregulated NEPC cell mouse models, as well patient samples. Phenotypically, overexpression increases sensitivity, represses genes, inhibits colony formation culture, xenograft tumor growth As expected, downregulates cells culture xenografts. Interestingly, signaling expression. In studying largely unclear mechanism underlying transcriptional repression by ADT, we found a target EZH2 epigenetic repression. Finally, genetic rescue experiments demonstrated through EZH2’s REST, which enhanced ADT-activated signaling. summary, our study revealed key pathway upregulation established novel relationships may also have implications other types neurobiology.

Language: Английский

Citations

5
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

12
Targeting the AURKB-MAD2L2 Axis Disrupts the DNA Damage Response and Glycolysis to Inhibit Colorectal Cancer Progression DOI Creative Commons

Shengjie Li,

Jiayou Ye,

K C Yang

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(2)

Published: Feb. 17, 2025

Dysregulated metabolic pathways, including glycolysis and a compromised DNA damage response (DDR), are linked to the progression of colorectal cancer (CRC). The mitotic arrest deficient-like 2 (MAD2L2) aurora kinase B (AURKB) genes play roles in cell cycle regulation DDR, making them potential targets for CRC therapy. Differential expression analysis was performed using Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COAD) GSE47074 datasets. A predictive model established, gene levels were further analyzed. Gene Expression Profiling Interaction Analysis database co-immunoprecipitation experiments assessed correlation between AURKB MAD2L2. Knockdown lines investigated role AURKB, followed by analyses behavior, oxidative stress, glycolysis, interaction with risk identified six prognostic (BUB1 checkpoint serine/threonine (BUB1B), (AURKA), exonuclease 1 (EXO1), topoisomerase II alpha (TOP2A), cyclin A2 (CCNA2)) associated CRC, which significantly expressed tumor samples from TCGA-COAD In vitro assays confirmed that knockdown inhibited induced G1 arrest, increased stress apoptosis. also impaired reducing lactate production, glucose uptake, ATP levels. Overexpression MAD2L2 partially reversed these effects, restored glycolytic activity, mitigated DDR caused knockdown. regulates modulating pathways. Targeting AURKB-MAD2L2 axis offers promising therapeutic strategy disrupting fundamental repair mechanisms CRC.

Language: Английский

Citations

0
Epigenetic abnormalities and neuroendocrine differentiation in prostate cancer DOI Creative Commons

G. Kovchenko,

А.В. Сивков, L. N. Lyubchenko

et al.

Siberian Journal of Oncology, Journal Year: 2025, Volume and Issue: 24(1), P. 115 - 124

Published: March 18, 2025

Objective . Unlike genetic changes, epigenetic aberrations in prostate cancer can be reversed under the influence of a chemical agent. This fact makes study changes an important object as potential therapeutic targets. Material and methods PubMed, Medline, eLibrary.ru databases were analyzed for keywords: cancer, lineage plasticity, neuroendocrine differentiation. For this literature review, 84 relevant publications selected. The review included studies from 1982 to 2024. Results most widely studied mutations are DNA hypo- hypermethylation, histone variability (methylation acetylation), Conclusion genomic landscape reveal new opportunities improving diagnosis therapy castration-resistant (CRPC), which is potentially lethal form disease. It not only search biomarkers identify disorders, but also optimal advanced cancer.

Language: Английский

Citations

0
A novel role for Neurog2 in MYCN driven neuroendocrine plasticity of prostate cancer DOI Creative Commons

Prachi Walke,

Jared D.W. Price,

Frederick S. Vizeacoumar

et al.

Oncogene, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Language: Английский

Citations

0