FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2955814384> ?p ?o ?g. }

• W2955814384 endingPage "4590" @default.
• W2955814384 startingPage "4590" @default.
• W2955814384 abstract "Abstract Previous work has demonstrated heterogeneity within collectively invading packs of lung cancer cells, including leader and follower cells that cooperate to facilitate invasion into the microenvironment. In order to better characterize the genetic differences between these two distinct cell types, we performed RNA-seq on purified populations of leader and follower cells from the H1299 non-small cell lung cancer cell line. Through this analysis, we identified that leaders and followers each contain distinct mutational and gene expression profiles, despite originating from the same parental cell line. Importantly, we identified 17 point mutations found uniquely in leaders and 18 point mutations found uniquely in followers, thus representing the first known compilation of leader- and follower-enriched genetic variants. Notable leader-enriched mutated genes included NAE1, NUP93 and ACTR3, while notable follower-enriched mutated genes included NADK, NDUFS1 and LEO1, suggesting possible roles for these genes in the biological function of leader and follower cells. After validating these mutations in the genomic DNA of leaders and followers, we sought to determine whether these mutational signatures are correlated with leader and follower gene expression markers within individual cells in a heterogeneous tumor cell population. To this end, we performed single-cell RNA-seq on H1299 parental, leader and follower cells isolated directly from collectively invading packs in a 3-D matrix. Hierarchical clustering and tSNE analysis based upon most variably expressed genes revealed four distinct cell clusters; two expressing higher levels of leader cell genes including MYO10 and JAG1 (clusters 1 and 4), and two expressing higher levels of follower genes including IL13RA2 and HTATIP2 (clusters 2 and 3). Interestingly, clusters 1 and 4 are composed exclusively of cells with leader mutational profiles, while nearly all cells in clusters 2 and 3 contain follower mutational profiles, suggesting that these mutations could be driving the differential gene expression, and ultimately the unique biological behaviors, of leaders and followers. In addition, clusters 1 and 2 display higher levels of proliferative markers compared with clusters 3 and 4, an indication that there are proliferative and non-proliferative subpopulations within the leader and follower populations. Taken together, these data give us new insight into the multiple levels of heterogeneity that exist within an invasive tumor cell population, suggest novel drivers of leader and follower cell biology in collective invasion, and open the door to new potential strategies for targeting and inhibiting metastasis in human lung cancer. Citation Format: Brian A. Pedro, Jessica Konen, Emily Summerbell, Janna K. Mouw, Manali Rupji, Bhakti Dwivedi, Jeanne Kowalski, Paula M. Vertino, Adam I. Marcus. Dissecting the biology of leader and follower cells in collective cancer invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4590." @default.
• W2955814384 created "2019-07-12" @default.
• W2955814384 creator A5019218539 @default.
• W2955814384 creator A5019366387 @default.
• W2955814384 creator A5024242252 @default.
• W2955814384 creator A5025069765 @default.
• W2955814384 creator A5032528540 @default.
• W2955814384 creator A5040229354 @default.
• W2955814384 creator A5042972439 @default.
• W2955814384 creator A5064924657 @default.
• W2955814384 creator A5065980494 @default.
• W2955814384 date "2019-07-01" @default.
• W2955814384 modified "2023-09-27" @default.
• W2955814384 title "Abstract 4590: Dissecting the biology of leader and follower cells in collective cancer invasion" @default.
• W2955814384 doi "https://doi.org/10.1158/1538-7445.am2019-4590" @default.
• W2955814384 hasPublicationYear "2019" @default.
• W2955814384 type Work @default.
• W2955814384 sameAs 2955814384 @default.
• W2955814384 citedByCount "0" @default.
• W2955814384 crossrefType "journal-article" @default.
• W2955814384 hasAuthorship W2955814384A5019218539 @default.
• W2955814384 hasAuthorship W2955814384A5019366387 @default.
• W2955814384 hasAuthorship W2955814384A5024242252 @default.
• W2955814384 hasAuthorship W2955814384A5025069765 @default.
• W2955814384 hasAuthorship W2955814384A5032528540 @default.
• W2955814384 hasAuthorship W2955814384A5040229354 @default.
• W2955814384 hasAuthorship W2955814384A5042972439 @default.
• W2955814384 hasAuthorship W2955814384A5064924657 @default.
• W2955814384 hasAuthorship W2955814384A5065980494 @default.
• W2955814384 hasBestOaLocation W29558143841 @default.
• W2955814384 hasConcept C104317684 @default.
• W2955814384 hasConcept C121608353 @default.
• W2955814384 hasConcept C144024400 @default.
• W2955814384 hasConcept C1491633281 @default.
• W2955814384 hasConcept C149923435 @default.
• W2955814384 hasConcept C189014844 @default.
• W2955814384 hasConcept C2908647359 @default.
• W2955814384 hasConcept C54355233 @default.
• W2955814384 hasConcept C86803240 @default.
• W2955814384 hasConcept C95444343 @default.
• W2955814384 hasConcept C96232424 @default.
• W2955814384 hasConceptScore W2955814384C104317684 @default.
• W2955814384 hasConceptScore W2955814384C121608353 @default.
• W2955814384 hasConceptScore W2955814384C144024400 @default.
• W2955814384 hasConceptScore W2955814384C1491633281 @default.
• W2955814384 hasConceptScore W2955814384C149923435 @default.
• W2955814384 hasConceptScore W2955814384C189014844 @default.
• W2955814384 hasConceptScore W2955814384C2908647359 @default.
• W2955814384 hasConceptScore W2955814384C54355233 @default.
• W2955814384 hasConceptScore W2955814384C86803240 @default.
• W2955814384 hasConceptScore W2955814384C95444343 @default.
• W2955814384 hasConceptScore W2955814384C96232424 @default.
• W2955814384 hasIssue "13_Supplement" @default.
• W2955814384 hasLocation W29558143841 @default.
• W2955814384 hasOpenAccess W2955814384 @default.
• W2955814384 hasPrimaryLocation W29558143841 @default.
• W2955814384 hasRelatedWork W1988393794 @default.
• W2955814384 hasRelatedWork W2078695526 @default.
• W2955814384 hasRelatedWork W2545003596 @default.
• W2955814384 hasRelatedWork W2884443433 @default.
• W2955814384 hasRelatedWork W2988567175 @default.
• W2955814384 hasRelatedWork W3045120309 @default.
• W2955814384 hasRelatedWork W3100339780 @default.
• W2955814384 hasRelatedWork W3128999657 @default.
• W2955814384 hasRelatedWork W4200187755 @default.
• W2955814384 hasRelatedWork W4220966885 @default.
• W2955814384 hasVolume "79" @default.
• W2955814384 isParatext "false" @default.
• W2955814384 isRetracted "false" @default.
• W2955814384 magId "2955814384" @default.
• W2955814384 workType "article" @default.