Fischer et al. reply

Fischer, Kari; Altorki, Nasser K.; Mittal, Vivek; Gao, Dingcheng

doi:10.1038/nature22817

Cited by 27 publications

(29 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar observations were obtained by using MMTV-Her2-driven breast tumors, or vimentin-driven Cre-mediated EMT lineage tracing models (9). These findings challenge the concept that EMT is required for metastasis, and have aroused vigorous discussion about its true contributions to metastasis (6,(10)(11)(12).…”

Section: Introductionsupporting

confidence: 65%

Differential Contributions of Pre- and Post-EMT Tumor Cells in Breast Cancer Metastasis

Lourenço

Crowley

et al. 2020

Cancer Research

Self Cite

View full text Add to dashboard Cite

◥ Metastases are responsible for the majority of breast cancerassociated deaths. The contribution of epithelial-to-mesenchymal transition (EMT) in the establishment of metastases is still controversial. To obtain in vivo evidence of EMT in metastasis, we established an EMT lineage tracing (Tri-PyMT) model, in which tumor cells undergoing EMT would irreversibly switch their fluorescent marker from RFP þ to GFP þ due to mesenchymal-specific Cre expression. Surprisingly, we found that lung metastases were predominantly derived from the epithelial compartment of breast tumors. However, concerns were raised on the fidelity and sensitivity of RFP-to-GFP switch of this model in reporting EMT of metastatic tumor cells. Here, we evaluated Tri-PyMT cells at the single-cell level using single-cell RNAsequencing and found that the Tri-PyMT cells exhibited a spectrum of EMT phenotypes, with EMT-related genes concomitantly expressed with the activation of GFP. The fluorescent color switch in these cells precisely marked an unequivocal change in EMT status, defining the pre-EMT and post-EMT compartments within the tumor. Consistently, the pre-EMT cells played dominant roles in metastasis, while the post-EMT cells were supportive in promoting tumor invasion and angiogenesis. Importantly, the post-EMT (GFP þ) cells in the Tri-PyMT model were not permanently committed to the mesenchymal phenotype; they were still capable of reverting to the epithelial phenotype and giving rise to secondary tumors, suggesting their persistent EMT plasticity. Our study addressed major concerns with the Tri-PyMT EMT lineage tracing model, which provides us with a powerful tool to investigate the dynamic EMT process in tumor biology. Significance: These findings confirm the fidelity and sensitivity of the EMT lineage tracing (Tri-PyMT) model and highlight the differential contributions of pre-and post-EMT tumor cells in breast cancer metastasis. See related commentary by Bunz, p.

show abstract

Section: Introductionsupporting

confidence: 65%

Differential Contributions of Pre- and Post-EMT Tumor Cells in Breast Cancer Metastasis

Lourenço

Crowley

et al. 2020

Cancer Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Importantly, none of the metastases observed were derived from these GFP+ EMT cells. Based on the specificity of their models, Fischer et al argued that EMT is not required for metastasis [32].…”

Section: Overview Of Epithelial and Mesenchymal Cscs In Breast Cancermentioning

confidence: 99%

CSCs in Breast Cancer—One Size Does Not Fit All: Therapeutic Advances in Targeting Heterogeneous Epithelial and Mesenchymal CSCs

Sulaiman

McGarry

Han

et al. 2019

Cancers

View full text Add to dashboard Cite

Unlike other breast cancer subtypes, triple-negative breast cancer (TNBC) has no specific targets and is characterized as one of the most aggressive subtypes of breast cancer that disproportionately accounts for the majority of breast cancer-related deaths. Current conventional chemotherapeutics target the bulk tumor population, but not the cancer stem cells (CSCs) that are capable of initiating new tumors to cause disease relapse. Recent studies have identified distinct epithelial-like (E) ALDH+ CSCs, mesenchymal-like (M) CD44+/CD24− CSCs, and hybrid E/M ALDH+/CD44+/CD24− CSCs. These subtypes of CSCs exhibit differential signal pathway regulations, possess plasticity, and respond differently to treatment. As such, co-inhibition of different subtypes of CSCs is key to viable therapy. This review serves to highlight different pathway regulations in E and M CSCs in TNBC, and to further describe their role in disease progression. Potential inhibitors targeting E and/or M CSCs based on clinical trials are summarized for further investigation. Since future research needs to adopt suitable tumor models and take into account the divergence of E and M CSCs for the development of effective treatments, TNBC models for clinically translatable studies are further discussed.

show abstract

“…In vitro, the estrogen knockdown reporter model of MCF-7 showed that the loss of ER expression was significantly associated with the EMT process, thereby promoting cell proliferation and migration by increasing the extracellular matrix and reducing matrix metalloproteases [27]. As such, EMT was thought to be an important step in carcinogenesis and the formation of distant metastasis [28,29]. In addition, the stem cell-like features induced by EMT were shown to contribute to drug resistance [30].…”

Section: Epithelial-to-mesenchymal Transition In Breast Cancermentioning

confidence: 99%

The Molecular Mechanism of Epithelial–Mesenchymal Transition for Breast Carcinogenesis

Chu

Yiang

et al. 2019

Biomolecules

View full text Add to dashboard Cite

The transforming growth factor-β (TGF-β) signaling pathway plays multiple regulatory roles in the tumorigenesis and development of cancer. TGF-β can inhibit the growth and proliferation of epithelial cells and induce apoptosis, thereby playing a role in inhibiting breast cancer. Therefore, the loss of response in epithelial cells that leads to the inhibition of cell proliferation due to TGF-β is a landmark event in tumorigenesis. As tumors progress, TGF-β can promote tumor cell invasion, metastasis, and drug resistance. At present, the above-mentioned role of TGF-β is related to the interaction of multiple signaling pathways in the cell, which can attenuate or abolish the inhibition of proliferation and apoptosis-promoting effects of TGF-β and enhance its promotion of tumor progression. This article focuses on the molecular mechanisms through which TGF-β interacts with multiple intracellular signaling pathways in tumor progression and the effects of these interactions on tumorigenesis.

show abstract

Fischer et al. reply

Cited by 27 publications

References 13 publications

Differential Contributions of Pre- and Post-EMT Tumor Cells in Breast Cancer Metastasis

Differential Contributions of Pre- and Post-EMT Tumor Cells in Breast Cancer Metastasis

CSCs in Breast Cancer—One Size Does Not Fit All: Therapeutic Advances in Targeting Heterogeneous Epithelial and Mesenchymal CSCs

The Molecular Mechanism of Epithelial–Mesenchymal Transition for Breast Carcinogenesis

Contact Info

Product

Resources

About