Tumor-suppressive effects of psoriasin (S100A7) are mediated through the β-catenin/T cell factor 4 protein pathway in estrogen receptor-positive breast cancer cells

Yadwinder S. Deol, Mohd W. Nasser, Lianbo Yu, Xianghong Zou, Ramesh K. Ganju

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Psoriasin (S100A7) is expressed in several epithelial malignancies including breast cancer. Although S100A7 is associated with the worst prognosis in estrogen receptor α-negative (ERα -) invasive breast cancers, its role in ERα-positive (ERα +) breast cancers is relatively unknown.Weinvestigated the significance of S100A7 in ERα + breast cancer cells and observed that S100A7 overexpression in ERα + breast cancer cells, MCF7 and T47D, exhibited decreased migration, proliferation, and wound healing. These results were confirmed in vivo in nude mouse model system. Mice injected with S100A7-overexpressing MCF7 cells showed significant reduction in tumor size compared with mice injected with vector control cells. Further mechanistic studies revealed that S100A7 mediates the tumor-suppressive effects via a coordinated regulation of the β-catenin/TCF4 pathway and an enhanced interaction of β-catenin and E-cadherin in S100A7-overexpressing ERα + breast cancer cells. We observed down-regulation of β-catenin, p-GSK3β, TCF4, cyclin D1, and c-myc in S100A7- overexpressing ERα + breast cancer cells. In addition, we observed increased expression of GSK3β. Treatment with GSK3β inhibitor CHIR 99021 increased the expression of β-catenin and its downstream target c-myc in S100A7-overexpressing cells. Tumors derived from mice injected with S100A7-overexpressing MCF7 cells also showed reduced activation of the β-catenin/TCF4 pathway. Therefore, our studies reveal for the first time that S100A7-overexpressing ERα + breast cancer cells exhibit tumor suppressor capabilities through down-modulation of the β-catenin/TCF4 pathway both in vitro and in vivo. Because S100A7 has been shown to enhance tumorigenicity in ERα - cells, our studies suggest that S100A7 may possess differential activities in ERα + compared with ERα - cells.

Original languageEnglish (US)
Pages (from-to)44845-44854
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number52
DOIs
StatePublished - Dec 30 2011

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Transcription Factor 7-Like 2 Protein
Catenins
Estrogen Receptors
Tumors
Cells
Breast Neoplasms
Neoplasms
MCF-7 Cells
Proteins
Cyclin D1
Cadherins
Chemical activation
Modulation
Nude Mice
Wound Healing
Down-Regulation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Tumor-suppressive effects of psoriasin (S100A7) are mediated through the β-catenin/T cell factor 4 protein pathway in estrogen receptor-positive breast cancer cells. / Deol, Yadwinder S.; Nasser, Mohd W.; Yu, Lianbo; Zou, Xianghong; Ganju, Ramesh K.

In: Journal of Biological Chemistry, Vol. 286, No. 52, 30.12.2011, p. 44845-44854.

Research output: Contribution to journalArticle

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abstract = "Psoriasin (S100A7) is expressed in several epithelial malignancies including breast cancer. Although S100A7 is associated with the worst prognosis in estrogen receptor α-negative (ERα -) invasive breast cancers, its role in ERα-positive (ERα +) breast cancers is relatively unknown.Weinvestigated the significance of S100A7 in ERα + breast cancer cells and observed that S100A7 overexpression in ERα + breast cancer cells, MCF7 and T47D, exhibited decreased migration, proliferation, and wound healing. These results were confirmed in vivo in nude mouse model system. Mice injected with S100A7-overexpressing MCF7 cells showed significant reduction in tumor size compared with mice injected with vector control cells. Further mechanistic studies revealed that S100A7 mediates the tumor-suppressive effects via a coordinated regulation of the β-catenin/TCF4 pathway and an enhanced interaction of β-catenin and E-cadherin in S100A7-overexpressing ERα + breast cancer cells. We observed down-regulation of β-catenin, p-GSK3β, TCF4, cyclin D1, and c-myc in S100A7- overexpressing ERα + breast cancer cells. In addition, we observed increased expression of GSK3β. Treatment with GSK3β inhibitor CHIR 99021 increased the expression of β-catenin and its downstream target c-myc in S100A7-overexpressing cells. Tumors derived from mice injected with S100A7-overexpressing MCF7 cells also showed reduced activation of the β-catenin/TCF4 pathway. Therefore, our studies reveal for the first time that S100A7-overexpressing ERα + breast cancer cells exhibit tumor suppressor capabilities through down-modulation of the β-catenin/TCF4 pathway both in vitro and in vivo. Because S100A7 has been shown to enhance tumorigenicity in ERα - cells, our studies suggest that S100A7 may possess differential activities in ERα + compared with ERα - cells.",
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AU - Ganju, Ramesh K.

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