Cancer heterogeneity and plasticity最新文献

{"title":"Combined Transcriptomic and Epitranscriptomic Profiling Identifies THBS1 as A Regulator of Enzalutamide Resistance in Prostate Cancer.","authors":"Emmanuelle Hodara, Lisa Swartz, Aubree Mades, Daniel Bsteh, Tong Xu, Suhn K Rhie, Amir Goldkorn","doi":"10.47248/chp2502020007","DOIUrl":"https://doi.org/10.47248/chp2502020007","url":null,"abstract":"<p><p>Cancer drug resistance arises not only from selection of resistant clones, but also through rapid activation of adaptive transcriptional programs. One mechanism of transcriptional regulation involves N6-methyladenosine (m⁶A) RNA modification, which dynamically regulates mRNA processing and alternative splicing, ultimately impacting cell fate and differentiation. In prostate cancer (PC), resistance to systemic therapies such as the androgen receptor pathway inhibitor (ARPI) enzalutamide is associated with a host of well-documented androgen receptor (AR) alterations, including amplification, mutation, and alternative splicing. Given these functions, we hypothesized that m⁶A modifications play a role in the transition to enzalutamide resistance in PC. To test this, we used methyl-RNA-immunoprecipitation followed by sequencing (MeRIP-seq) in parallel with RNA-seq to identify gene transcripts that were both differentially methylated and differentially expressed between enzalutamide-sensitive and enzalutamide-resistant PC cells. We filtered and prioritized these genes using clinical and functional database tools, including Gene Ontology (GO) enrichment analysis and Gene Set Enrichment Analysis (GSEA), The Cancer Genome Atlas (TCGA), and the Oncology Research Information Network (ORIEN) avatar. Using this approach, we identified 487 transcripts that were both differentially methylated and differentially expressed and validated six of the top 12 candidates via targeted qPCR and MeRIP-PCR. One of these, <i>THBS1</i>, was found to have increased m⁶A level associated with decreased transcript levels in enzalutamide-resistant cells, a finding recapitulated in publicly available preclinical and clinical data. Moreover, in enzalutamide-sensitive cells, depletion of <i>THBS1</i> by siRNA-knockdown induced resistance to enzalutamide. While <i>THBS1</i> has previously been implicated in aggressive PC phenotypes, we now show that <i>THBS1</i> downregulation directly contributes to a rapid transition to enzalutamide resistance, suggesting a novel role for this gene in PC hormonal therapy resistance. These results constitute the first comprehensive epitranscriptomic profiling of ARPI resistance and identify <i>THBS1</i> as a potential driver of acute resistance in prostate cancer.</p>","PeriodicalId":520023,"journal":{"name":"Cancer heterogeneity and plasticity","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Single-Cell Techniques for Linking Phenotypes to Genotypes.","authors":"Hsiao-Chun Chen, Yushu Ma, Jinxiong Cheng, Yu-Chih Chen","doi":"10.47248/chp2401010004","DOIUrl":"10.47248/chp2401010004","url":null,"abstract":"<p><p>Single-cell analysis has become an essential tool in modern biological research, providing unprecedented insights into cellular behavior and heterogeneity. By examining individual cells, this approach surpasses conventional population-based methods, revealing critical variations in cellular states, responses to environmental cues, and molecular signatures. In the context of cancer, with its diverse cell populations, single-cell analysis is critical for investigating tumor evolution, metastasis, and therapy resistance. Understanding the phenotype-genotype relationship at the single-cell level is crucial for deciphering the molecular mechanisms driving tumor development and progression. This review highlights innovative strategies for selective cell isolation based on desired phenotypes, including robotic aspiration, laser detachment, microraft arrays, optical traps, and droplet-based microfluidic systems. These advanced tools facilitate high-throughput single-cell phenotypic analysis and sorting, enabling the identification and characterization of specific cell subsets, thereby advancing therapeutic innovations in cancer and other diseases.</p>","PeriodicalId":520023,"journal":{"name":"Cancer heterogeneity and plasticity","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11328949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unmasking SMLR1: The hidden player in colorectal cancer's liver metastasis.","authors":"Xiaozhuo Liu","doi":"10.47248/chp2401010002","DOIUrl":"https://doi.org/10.47248/chp2401010002","url":null,"abstract":"","PeriodicalId":520023,"journal":{"name":"Cancer heterogeneity and plasticity","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Cancer Heterogeneity and Plasticity</i> - A new journal dedicated to understanding cancer cell states and interactions with the tumor microenvironment.","authors":"Dean G Tang","doi":"10.47248/chp2401010001","DOIUrl":"10.47248/chp2401010001","url":null,"abstract":"","PeriodicalId":520023,"journal":{"name":"Cancer heterogeneity and plasticity","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment-induced stemness and lineage plasticity in driving prostate cancer therapy resistance.","authors":"Anmbreen Jamroze, Xiaozhuo Liu, Dean G Tang","doi":"10.47248/chp2401010005","DOIUrl":"10.47248/chp2401010005","url":null,"abstract":"<p><p>Most human cancers are heterogeneous consisting of cancer cells at different epigenetic and transcriptional states and with distinct phenotypes, functions, and drug sensitivities. This inherent cancer cell heterogeneity contributes to tumor resistance to clinical treatment, especially the molecularly targeted therapies such as tyrosine kinase inhibitors (TKIs) and androgen receptor signaling inhibitors (ARSIs). Therapeutic interventions, in turn, induce lineage plasticity (also called lineage infidelity) in cancer cells that also drives therapy resistance. In this Perspective, we focus our discussions on cancer cell lineage plasticity manifested as treatment-induced switching of epithelial cancer cells to basal/stem-like, mesenchymal, and neural lineages. We employ prostate cancer (PCa) as the prime example to highlight ARSI-induced lineage plasticity during and towards development of castration-resistant PCa (CRPC). We further discuss how the tumor microenvironment (TME) influences therapy-induced lineage plasticity. Finally, we offer an updated summary on the regulators and mechanisms driving cancer cell lineage infidelity, which should be therapeutically targeted to extend the therapeutic window and improve patients' survival.</p>","PeriodicalId":520023,"journal":{"name":"Cancer heterogeneity and plasticity","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}