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Inflammatory breast cancer cells are characterized by abrogated TGFβ1-dependent cell motility and SMAD3 activity.

Publication ,  Journal Article
Rypens, C; Marsan, M; Van Berckelaer, C; Billiet, C; Melis, K; Lopez, SP; van Dam, P; Devi, GR; Finetti, P; Ueno, NT; Bertucci, F; Dirix, P ...
Published in: Breast Cancer Res Treat
April 2020

PURPOSE: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with elevated metastatic potential, characterized by tumor emboli in dermal and parenchymal lymph vessels. This study has investigated the hypothesis that TGFβ signaling is implicated in the molecular biology of IBC. METHODS: TGFβ1-induced cell motility and gene expression patterns were investigated in three IBC and three non-IBC (nIBC) cell lines. Tissue samples from IBC and nIBC patients were investigated for the expression of nuclear SMAD2, SMAD3, and SMAD4. SMAD protein levels were related to gene expression data. RESULTS: TGFβ1-induced cell motility was strongly abrogated in IBC cells (P = 0.003). Genes differentially expressed between IBC and nIBC cells post TGFβ1 exposure revealed attenuated expression of SMAD3 transcriptional regulators, but overexpression of MYC target genes in IBC. IBC patient samples demonstrated a near absence of SMAD3 and -4 expression in the primary tumor compared to nIBC patient samples (P < 0.001) and a further reduction of staining intensity in tumor emboli. Integration of gene and protein expression data revealed that a substantial fraction of the IBC signature genes correlated with SMAD3 and these genes are indicative of attenuated SMAD3 signaling in IBC. CONCLUSION: We demonstrate attenuated SMAD3 transcriptional activity and SMAD protein expression in IBC, together with obliterated TGFβ1-induced IBC cell motility. The further reduction of nuclear SMAD expression levels in tumor emboli suggests that the activity of these transcription factors is involved in the metastatic dissemination of IBC cells, possibly by enabling collective invasion after partial EMT.

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Published In

Breast Cancer Res Treat

DOI

EISSN

1573-7217

Publication Date

April 2020

Volume

180

Issue

2

Start / End Page

385 / 395

Location

Netherlands

Related Subject Headings

  • Transforming Growth Factor beta1
  • Smad3 Protein
  • Signal Transduction
  • Proto-Oncogene Proteins c-myc
  • Oncology & Carcinogenesis
  • Inflammatory Breast Neoplasms
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Female
 

Citation

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Rypens, C., Marsan, M., Van Berckelaer, C., Billiet, C., Melis, K., Lopez, S. P., … Van Laere, S. J. (2020). Inflammatory breast cancer cells are characterized by abrogated TGFβ1-dependent cell motility and SMAD3 activity. Breast Cancer Res Treat, 180(2), 385–395. https://doi.org/10.1007/s10549-020-05571-z
Rypens, Charlotte, Melike Marsan, Christophe Van Berckelaer, Charlotte Billiet, Kirsten Melis, Sara Perez Lopez, Peter van Dam, et al. “Inflammatory breast cancer cells are characterized by abrogated TGFβ1-dependent cell motility and SMAD3 activity.Breast Cancer Res Treat 180, no. 2 (April 2020): 385–95. https://doi.org/10.1007/s10549-020-05571-z.
Rypens C, Marsan M, Van Berckelaer C, Billiet C, Melis K, Lopez SP, et al. Inflammatory breast cancer cells are characterized by abrogated TGFβ1-dependent cell motility and SMAD3 activity. Breast Cancer Res Treat. 2020 Apr;180(2):385–95.
Rypens, Charlotte, et al. “Inflammatory breast cancer cells are characterized by abrogated TGFβ1-dependent cell motility and SMAD3 activity.Breast Cancer Res Treat, vol. 180, no. 2, Apr. 2020, pp. 385–95. Pubmed, doi:10.1007/s10549-020-05571-z.
Rypens C, Marsan M, Van Berckelaer C, Billiet C, Melis K, Lopez SP, van Dam P, Devi GR, Finetti P, Ueno NT, Bertucci F, Dirix P, Neven P, Vermeulen P, Dirix L, Van Laere SJ. Inflammatory breast cancer cells are characterized by abrogated TGFβ1-dependent cell motility and SMAD3 activity. Breast Cancer Res Treat. 2020 Apr;180(2):385–395.
Journal cover image

Published In

Breast Cancer Res Treat

DOI

EISSN

1573-7217

Publication Date

April 2020

Volume

180

Issue

2

Start / End Page

385 / 395

Location

Netherlands

Related Subject Headings

  • Transforming Growth Factor beta1
  • Smad3 Protein
  • Signal Transduction
  • Proto-Oncogene Proteins c-myc
  • Oncology & Carcinogenesis
  • Inflammatory Breast Neoplasms
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Female