TGF-β protects dormant metastasis from immune mechanosurveillance
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1123643 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29397540_1.fastq.gz | Fastqsanger.gz | |||
| SRR29397540_2.fastq.gz | Fastqsanger.gz | |||
| SRR29397541_1.fastq.gz | Fastqsanger.gz | |||
| SRR29397541_2.fastq.gz | Fastqsanger.gz | |||
| SRR29397542_1.fastq.gz | Fastqsanger.gz |
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Project description:To explore the regulatory role of 14-3-3ζ in TGF-β induced bone metastasis program in 231 cells, we generated MDA-MB-231 human breast cancer cell sublines with 14-3-3ζ shRNA knockdown (231.ZKD-4 and 231.ZKD-5) and scrambled shRNA (231.Scr) We performed cDNA microarray analysis on these cells treated with vehicle or TGF-β (5ng/ml, 2 hours) respectively in vitro Total RNA were extracted from 231.scr, 231.ZKD-4, 231.ZKD-5 cells treated with vehicle or TGF-β, and subjected to illumina Human HT-12 v4 arrays analysis
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Project description:Purpose: Presence of pelvic lymph node metastases is the main prognostic factor in early stage cervical cancer patients, primarily treated with surgery. Aim of this study was to identify cellular tumor pathways associated with pelvic lymph node metastasis in early stage cervical cancer. Experimental Design: Gene expression profiles (Affymetrix U133 plus 2.0) of 20 patients with negative (N0) and 19 with positive lymph nodes (N+), were compared with gene sets that represent all 285 presently available pathway signatures. Validation immunostaining of tumors of 274 consecutive early stage cervical cancer patients was performed for representatives of the identified pathways. Results: Analysis of 285 pathways resulted in identification of five pathways (TGF-β, NFAT, ALK, BAD, and PAR1) that were dysregulated in the N0, and two pathways (β-catenin and Glycosphingolipid Biosynthesis Neo Lactoseries) in the N+ group. Class comparison analysis revealed that five of 149 genes that were most significantly differentially expressed between N0 and N+ tumors (P<0.001) were involved in β-catenin signaling (TCF4, CTNNAL1, CTNND1/p120, DKK3 and WNT5a). Immunohistochemical validation of two well-known cellular tumor pathways (TGF-β and β-catenin) confirmed that the TGF-β pathway (positivity of Smad4) was related to N0 (OR:0.20, 95%CI:0.06-0.66) and the β-catenin pathway (p120 positivity) to N+ (OR:1.79, 95%CI:1.05-3.05). Conclusions: Our study provides new, validated insights in the molecular mechanism of lymph node metastasis in cervical cancer. Pathway analysis of the microarray expression profile suggested that the TGF-β and p120-associated non-canonical β-catenin pathways are important in pelvic lymph node metastasis in early stage cervical cancer. For the microarray experiment, we selected fresh frozen primary cervical cancer tissue, containing at least 80% tumor cells, of patients with histologically confirmed N0 (n=20) and of patients with N+ (n=19). The N0 and N+ groups were matched for age, FIGO stage and histology (all squamous cell carcinoma).
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