Fibronectin extra domain A suppresses apoptosis of colorectal cancer SW480 cells by inhibiting P53 nuclear translocation

Weiwen Yang; Yue Zhang; Xiong Xie; Juanjuan Ou; Houjie Liang; Xueli Pang

doi:10.16016/j.1000-5404.201610068

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Fibronectin extra domain A suppresses apoptosis of colorectal cancer SW480 cells by inhibiting P53 nuclear translocation

更新时间：2026-01-09

- Fibronectin extra domain A suppresses apoptosis of colorectal cancer SW480 cells by inhibiting P53 nuclear translocation
- Journal of Third Military Medical University Vol. 39, Issue 8, Pages: 787-793(2017)
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.201610068
  CLC：
- Published：2017-04
- 稿件说明：
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Weiwen Yang, Yue Zhang, Xiong Xie, et al. Fibronectin extra domain A suppresses apoptosis of colorectal cancer SW480 cells by inhibiting P53 nuclear translocation[J]. Journal of Third Military Medical University, 2017, 39(8): 787-793.
DOI：

Weiwen Yang, Yue Zhang, Xiong Xie, et al. Fibronectin extra domain A suppresses apoptosis of colorectal cancer SW480 cells by inhibiting P53 nuclear translocation[J]. Journal of Third Military Medical University, 2017, 39(8): 787-793. DOI： 10.16016/j.1000-5404.201610068.

摘要

Abstract

Objective

To investigate the role of fibronectin extra domain a (FN-EDA) in regulating the apoptosis of colorectal cancer cells and explore the possible mechanism.

Methods

Gene set enrichment analysis (GSEA) was used to analyze the microarray data of colorectal cancer with high and low FN-EDA expression. In a colorectal cancer cell line SW480 with lentiviral vector-mediated FN-EDA knockdown

the transcription levels of

P53

BAX

and

P 21

were assayed using real-time PCR

and the protein expression levels of P53

BAX

P21

Cleaved caspase-3

p-P53 (Ser15)

p-P53 (Ser37) and p-P53 (Ser392) were detected with Western blotting. Flow cytometry was used to detect the changes of cell apoptosis following FN-EDA knockdown

and the subcellular distribution of P53 was observed by immunofluorescence assay; the interaction between FN-EDA and P53 was analyzed using co-immunoprecipitation assay.

Results

The genesets of KEGG_APOPTOSIS were obviously enriched and up-regulated in colorectal canc

er cells with low FN-EDA expression (

0.05). Compared with the control cells

the cells with FN-EDA knockdown showed significantly increased protein levels of P53

BAX

P21

Cleaved caspase-3

p-P53 (Ser15)

p-P53 (Ser37) and p-P53 (Ser392) with also increased apoptotic rate (

0.05); FN-EDA knockdown also resulted in significantly increased nuclear translocation of P53 as shown by immunofluorescence assay and Western blotting. Over-expression of FN-EDA in the cells with FN-EDA knockdown significantly inhibited the cell apoptosis (

0.05)

induced down-regulation of P53

p-P53 (Ser15)

p-P53 (Ser37) and BAX

and decreased nuclear translocation of P53. Co-immunoprecipitation assay showed a direct interaction between P53 and FN-EDA.

Conclusion

FN-EDA inhibits nuclear traslocation and phosphrylation of P53

via

a direct interaction with P53 to regulate P53-BAX pathway and suppress the apoptosis of colorectal cancer SW480 cells.

关键词

Keywords

references

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