Association of ZEB1 and Vimentin with poor prognosis in metaplastic breast cancer

Zawati, Imen; Jlassi, Aida; Adouni, Olfa; Nouira, Meriem; Manai, Maroua; Rahal, Khaled; Driss, Mohamed Ridha; Manaï, Mohamed

doi:10.1016/j.anndiagpath.2022.151954

Cited by 8 publications

(6 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Metaplastic carcinoma of the breast, although rare, is more common in AA women compared to EA women 13 . Our results indicate that PZP cells are the cell-of-origin of this cancer type.…”

Section: Discussionmentioning

confidence: 99%

Influence of genetic ancestry on breast stromal cells provides biologic basis for increased incidence of metaplastic breast cancer in women of African descent

Kumar

Batic

Bhat‐Nakshatri

et al. 2022

Preprint

View full text Add to dashboard Cite

The biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to the ductal epithelial cells in the normal breast of women of African Ancestry (AA) compared to European Ancestry (EA). By establishing and characterizing cell lines corresponding to these cells and validating in vitro findings with tissue microarrays of healthy breast tissue from AA, EA and Latina Ancestry (LA) women, we demonstrate that these cells have the properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFRalpha;. PROCR+/ZEB1+/PDGFRalpha+ cells, hence renamed as PZP cells, are enriched in the normal breast tissues of AA compared to EA or LA women. In vitro, PZP cells trans-differentiated into adipocytes or osteocytes. In co-culture conditions, PZP:epithelial cell communication resulted in luminal epithelial cells acquiring basal/stem cell characteristics and increased expression of IL-6 suggesting the impact of this communication on breast epithelial hierarchy and the microenvironment. Consistent with this possibility, the level of phospho-STAT3, which is a downstream target of IL-6, was higher in the normal and cancerous breast tissues of AA compared to EA women. PZP cells transformed with HRasG12V with or without SV40-T/t antigens generated metaplastic carcinoma in NSG mice suggesting that these cells could be the cell-of-origin of metaplastic breast cancers. Collectively, these results identify a stromal cell component that could influence the biology of breast cancer in AA women.

show abstract

“…Metaplastic carcinoma of the breast, although rare, is more common in AA women compared to EA women 13 . Our results indicate that PZP cells are the cell-of-origin of this cancer type.…”

Section: Discussionmentioning

confidence: 99%

Influence of genetic ancestry on breast stromal cells provides biologic basis for increased incidence of metaplastic breast cancer in women of African descent

Kumar

Batic

Bhat‐Nakshatri

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…However, it is worth noting that the level of miR-223-3p in patients with invasive ductal carcinoma is higher than that in patients with ductal carcinoma in situ, suggesting that use of miR-223 as a biomarker in these cases is still controversial 57 . There have been many reports about the high expression of ZEB1 and the poor prognosis of breast cancer patients 58 . It is reported that YEATS4 regulates the expression of ZEB1 in breast cancer, promotes EMT and metastasis, and is related to poor prognosis 59 .…”

Section: Discussionmentioning

confidence: 99%

NOTCH3 inhibits transcription factor ZEB1 expression and metastasis of breast cancer cells via transcriptionally upregulating miR-223

Chen,

Zhong,

et al. 2024

J. Cancer

View full text Add to dashboard Cite

Background: NOTCH receptor 3 (NOTCH3) and zinc finger E-box binding protein 1 (ZEB1) play important roles in breast cancer respectively. NOTCH3 maintains the luminal phenotype and inhibits epithelial-mesenchymal transition (EMT) in breast cancer, while ZEB1 and NOTCH3 have the opposite effects. Methods: Public databases were used to predict the expression of NOTCH3 and ZEB1 in breast cancer cell lines. The regulatory effect of NOTCH3 on ZEB1 expression was verified by western blot and RT-PCR. MiRNAs regulating ZEB1 expression were identified by using multiple databases and confirmed by reporter gene experiments. Cellular function experiments were conducted to evaluate the role of NOTCH3/miR-223/ZEB1 in the proliferation and invasion of triple-negative breast cancer (TNBC). Results: NOTCH3 and ZEB1 have opposite expression pattern in MCF-7 cells that over-express LncATB or were incubated in TGF-β to induce EMT. Western blotting and RT-PCR showed that NOTCH3 could regulate expression of ZEB1. MiR-223 inhibited the proliferation and invasion of breast cancer cells via down-regulating the expression of ZEB1. NOTCH3 inhibited the proliferation and invasion of breast cancer cells via up-regulating the expression of miR-223. Clinically, high expression of NOTCH3, miR-223 or low expression of ZEB1 were related to good prognosis of breast cancer patients. Conclusion: The current study reports a novel NOTCH3/miR-223/ZEB1 axis, which can inhibit the proliferation and invasion of breast cancer cells, and may serve as a potential biomarker for the prognosis of breast cancer.

show abstract

“…Metaplastic carcinoma of the breast, although rare, is more common in AA women compared to EA women 13 whose levels in the tissue microenvironment could be influenced due to PZP-epithelial cell interaction, there may be additional signaling pathway activation as a consequence of this interaction and potentially influence the microenvironment. Because of the ability of PZP cells to influence signaling in epithelial cells and differences in their number based on genetic ancestry, signaling pathway in epithelial cells of the breast may show genetic ancestry-dependent variability in signaling under both normal and cancerous condition and drugs that target crosstalk between these two cell types can be new therapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

“…Stromal ZEB1 expression in breast cancer inversely correlates with abundance of multiple immune cell types 10 . ZEB1 expression has been linked to claudin-low and metaplastic breast cancer subtypes, both of which are more common in AA compared to EA women 11,12,13,14 . These observations prompted us to further characterize stromally located ZEB1 + cells for their potential role in breast cancer initiation and progression within the context of genetic ancestry.…”

Section: Introductionmentioning

confidence: 99%

Influence of genetic ancestry on breast stromal cells provides biologic basis for increased incidence of metaplastic breast cancer in women of African descent

Kumar¹,

Batic

Bhat‐Nakshatri

et al. 2022

Preprint

View full text Add to dashboard Cite

The biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to the ductal epithelial cells in the normal breast of women of African Ancestry (AA) compared to European Ancestry (EA). By establishing and characterizing cell lines corresponding to these cells and validating in vitro findings with tissue microarrays of healthy breast tissue from AA, EA and Latina Ancestry (LA) women, we demonstrate that these cells have the properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFRa. PROCR+/ZEB1+/PDGFRa+ cells, hence renamed as PZP cells, are enriched in the normal breast tissues of AA compared to EA or LA women. In vitro, PZP cells trans-differentiated into adipocytes or osteocytes. In co-culture conditions, PZP:epithelial cell communication resulted in luminal epithelial cells acquiring basal/stem cell characteristics and increased expression of IL-6 suggesting the impact of this communication on breast epithelial hierarchy and the microenvironment. Consistent with this possibility, the level of phosphoSTAT3, which is a downstream target of IL-6, was higher in the normal and cancerous breast tissues of AA compared to EA women. PZP cells transformed with HRasG12V ± SV40-T/t antigens generated metaplastic carcinoma in NSG mice suggesting that these cells could be the cell-of-origin of metaplastic breast cancers. Collectively, these results identify a stromal cell component that could influence the biology of breast cancer in AA women.

show abstract

Association of ZEB1 and Vimentin with poor prognosis in metaplastic breast cancer

Cited by 8 publications

References 30 publications

Influence of genetic ancestry on breast stromal cells provides biologic basis for increased incidence of metaplastic breast cancer in women of African descent

Influence of genetic ancestry on breast stromal cells provides biologic basis for increased incidence of metaplastic breast cancer in women of African descent

NOTCH3 inhibits transcription factor ZEB1 expression and metastasis of breast cancer cells via transcriptionally upregulating miR-223

Influence of genetic ancestry on breast stromal cells provides biologic basis for increased incidence of metaplastic breast cancer in women of African descent

Contact Info

Product

Resources

About