PUBLICATION

p62/SQSTM1 interacts with vimentin to enhance breast cancer metastasis

Authors
Li, S.S., Xu, L.Z., Zhou, W., Yao, S., Wang, C.L., Xia, J.L., Wang, H.F., Kamran, M., Xue, X.Y., Dong, L., Wang, J., Ding, X.D., Bella, L., Bugeon, L., Xu, J., Zheng, F.M., Dallman, M.J., Lam, E.W., Liu, Q.
ID
ZDB-PUB-171003-1
Date
2017
Source
Carcinogenesis   38(11): 1092-1103 (Journal)
Registered Authors
Bugeon, Laurence, Dallman, Maggie, Zhou, Wei
Keywords
Breast cancer, metastasis, p62, protein interaction, vimentin
MeSH Terms
  • Zebrafish
  • Cell Movement/physiology
  • Mice, Nude
  • Cell Line, Tumor
  • Neoplasm Invasiveness/pathology
  • Down-Regulation/physiology
  • Female
  • Mice, Inbred BALB C
  • Up-Regulation/physiology
  • Humans
  • Sequestosome-1 Protein/genetics*
  • Neoplasm Metastasis/pathology*
  • Neoplasm Recurrence, Local/metabolism
  • Neoplasm Recurrence, Local/pathology
  • Gene Expression Regulation, Neoplastic/physiology
  • MCF-7 Cells
  • HEK293 Cells
  • Animals
  • Breast Neoplasms/metabolism*
  • Breast Neoplasms/pathology*
  • Vimentin/metabolism*
  • Mice
(all 22)
PubMed
28968743 Full text @ Carcinogenesis
Abstract
The signalling adaptor p62 is frequently overexpressed in numerous cancer types. Here, we found that p62 expression was elevated in metastatic breast cancer and its overexpression correlated with reduced metastasis-free and relapse-free survival times. Analysis of p62 expression in breast cancer cell lines demonstrated that high p62 expression was associated with the invasive phenotypes of breast cancer. Indeed, silencing p62 expression attenuated the invasive phenotypes of highly metastatic cells, whereas overexpressing p62 promoted the invasion of non-metastatic cells in in vitro microfluidic model. Moreover, MDA-MB-231 cells with p62 depletion which were grown in a three-dimensional culture system exhibited a loss of invasive protrusions. Consistently, genetic ablation of p62 suppressed breast cancer metastasis in both zebrafish embryo and immunodeficient mouse models, as well as decreased tumorigenicity in vivo. To explore the molecular mechanism by which p62 promotes breast cancer invasion, we performed a co-immunoprecipitation (co-IP)-MS analysis and revealed that p62 interacted with vimentin, which mediated the function of p62 in promoting breast cancer invasion. Vimentin protein expression was downregulated upon p62 suppression and upregulated with p62 overexpression in breast cancer cells. Linear regression analysis of clinical breast cancer specimens showed a positive correlation between p62 and vimentin protein expression. Together, our findings provide strong evidence that p62 functions as a tumour metastasis promoter by binding vimentin and promoting its expression. This finding might help to develop novel molecular therapeutic strategies for breast cancer metastasis treatment.
Genes / Markers
Figures
Figure Gallery (1 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b18
    		Small Deletion
    w2
      		Point Mutation
      1 - 2 of 2
      Show
      Human Disease / Model
      Human Disease Fish Conditions Evidence
      breast cancermitfaw2/w2; mpv17b18/b18cancer xenotransplantationTAS
      1 - 1 of 1
      Show
      Sequence Targeting Reagents
      No data available
      Fish
      Fish
      mitfaw2/w2; mpv17b18/b18
      1 - 1 of 1
      Show
      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      No data available
      Mapping
      No data available
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      Citation
      Li, S.S., Xu, L.Z., Zhou, W., Yao, S., Wang, C.L., Xia, J.L., Wang, H.F., Kamran, M., Xue, X.Y., Dong, L., Wang, J., Ding, X.D., Bella, L., Bugeon, L., Xu, J., Zheng, F.M., Dallman, M.J., Lam, E.W., Liu, Q. (2017) p62/SQSTM1 interacts with vimentin to enhance breast cancer metastasis. Carcinogenesis. 38(11):1092-1103.