Proc. Natl. Acad. Sci. U.S.A.
 2016
DOI: 10.1073/pnas.1508541113
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Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters

Kevin J. Cheung
1
,
Veena Padmanaban
2
,
Vanesa L. Silvestri
3
et al.

Abstract: Recent genomic studies challenge the conventional model that each metastasis must arise from a single tumor cell and instead reveal that metastases can be composed of multiple genetically distinct clones. These intriguing observations raise the question: How do polyclonal metastases emerge from the primary tumor? In this study, we used multicolor lineage tracing to demonstrate that polyclonal seeding by cell clusters is a frequent mechanism in a common mouse model of breast cancer, accounting for >90% of metas… Show more

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Cited by 744 publications

(842 citation statements)
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“…1E, Supplementary Fig. S2A-E), which is consistent with previous reports from cell lines (5) and mouse tumor models (28). CTC clusters in the blood were detected at similar frequencies (8–10% clustered events) between patients (n=7 patients, 15 blood specimens) and PDX models (n=4 models, 7 blood specimens) (Fig.…”
Section: Resultssupporting
confidence: 92%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
“…1E, Supplementary Fig. S2A-E), which is consistent with previous reports from cell lines (5) and mouse tumor models (28). CTC clusters in the blood were detected at similar frequencies (8–10% clustered events) between patients (n=7 patients, 15 blood specimens) and PDX models (n=4 models, 7 blood specimens) (Fig.…”
Section: Resultssupporting
confidence: 92%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
“…Gene set enrichment analysis (GSEA) of differentially expressed genes further supported these findings, showing higher mRNA levels of desmosome-related genes in 4T1 WT cells compared to 4T1 ApoA1 cells (Fig. 3 h, i), which is in line with previous reports linking KRT14 expression to desmosome adhesion complex genes [ 35 ]. At the protein level, transfection of ApoA1-overexpressing plasmid in HCC1937, MDA-MB231, and 4T1 cells resulted in a significant reduction in KRT14 expression (Fig.…”
Section: Resultssupporting
confidence: 91%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
“…In the current study, we found that MHC-II expression is upregulated in KRT14-reduced TNBC, consistent with a previous study showing that KRT14 was correlated with MHC class II antigen presentation protein complexes (MHC-II) in TNBC 37 . Given that MHC-II expression determines the activation of CD4+ T cells [54][55][56][57] and/or its downstream effect, e.g.…”
Section: Discussionsupporting
confidence: 93%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
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