scholarly journals Decrease of lactogenic hormones induce epithelial-mesenchymal transition via TGFβ1 and arachidonic acid during mammary gland involution

2017 ◽  
Vol 63 (3) ◽  
pp. 325-332 ◽  
Author(s):  
Haolin ZHANG ◽  
Yuning LIU ◽  
Ji WENG ◽  
Kento USUDA ◽  
Kazuki FUJII ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Mammary Gland ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Mammary Gland Involution ◽  
Lactogenic Hormones

scholarly journals An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis

2020 ◽  
Author(s):  
Molly M. Wilson ◽  
Céline Callens ◽  
Matthieu Le Gallo ◽  
Svetlana Mironov ◽  
Qiong Ding ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Molecular Mechanisms ◽  
Mammary Gland Development ◽  
Epithelial Mesenchymal Transition ◽  
Gene Expression Signature ◽  
Normal Mammary Gland ◽  
Breast Cancers ◽  
Tumor Initiating Cells ◽  
Mesenchymal Transition ◽  
Gland Development

AbstractThe Epithelial–Mesenchymal Transition (EMT) and primary ciliogenesis induce stem cell properties in basal Mammary Stem Cells (MaSCs) to promote mammogenesis, but the underlying mechanisms remain incompletely understood. Here, we show that EMT transcription factors promote ciliogenesis at intermediate EMT transition states by activating ciliogenesis inducers, including FGFR1. The resulting primary cilia promote BBS11-dependent ubiquitination and inactivation of a central signaling node, GLIS2. We show that GLIS2 inactivation promotes MaSC stemness, and GLIS2 is required for normal mammary gland development. Moreover, GLIS2 inactivation is required to induce the proliferative and tumorigenic capacities of the Mammary-Tumor-initiating cells (MaTICs) of claudin-low breast cancers. Claudin-low breast tumors can be segregated from other breast tumor subtypes based on a GLIS2-dependent gene expression signature. Collectively, our findings establish molecular mechanisms by which EMT programs induce ciliogenesis to control MaSC and MaTIC biology, mammary gland development, and claudin-low breast cancer formation.

scholarly journals Inactivation of RARβ Inhibits Wnt1-induced Mammary Tumorigenesis by Suppressing Epithelial-mesenchymal Transitions

2014 ◽  
Vol 12 (1) ◽  
pp. nrs.12004 ◽  
Author(s):  
Xingxing Liu ◽  
Vincent Giguère
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Epithelial Mesenchymal Transition ◽  
Integration Site ◽  
Mammary Tumorigenesis ◽  
Tumor Growth Rate ◽  
Cancer Associated Fibroblasts ◽  
Stromal Compartment ◽  
Mesenchymal Transition ◽  
Retinoid Signaling

Retinoic acid receptor β (RARβ) has been proposed to act as a tumor suppressor in breast cancer. In contrast, recent data have shown that RARβ promotes ERBB2-induced mammary gland tumorigenesis through remodeling of the stromal compartment and activation of cancer-associated fibroblasts. However, it is currently unknown whether RARβ oncogenic activity is specific to ERBB2-induced tumors, or whether it influences the initiation and progression of other breast cancer subtypes. Accordingly, we set out to investigate the involvement of RARβ in basal-like breast cancer using mouse mammary tumor virus (MMTV)-wingless-related integration site 1 (Wnt1)-induced mammary gland tumorigenesis as a model system. We found that compared with wild type mice, inactivation of Rarb resulted in a lengthy delay in Wnt1-induced mammary gland tumorigenesis and in a significantly slower tumor growth rate. Ablation of Rarb altered the composition of the stroma, repressed the activation of cancer-associated fibroblasts, and reduced the recruitment of inflammatory cells and angiogenesis. Reduced expression of IGF-1 and activity of its downstream signaling pathway contribute to attenuate EMT in the Rarb-null tumors. Our results show that, in the absence of retinoid signaling via RARβ, reduced IGF-1 signaling results in suppression of epithelial-mesenchymal transition and delays tumorigenesis induced by the Wnt1 oncogene. Accordingly, our work reinforces the concept that antagonizing RARβ-dependent retinoid signaling could provide a therapeutic avenue to treat poor outcome breast cancers.

scholarly journals Differential effects of Pax3 on expression of polysialyltransferases STX and PST in TGF-β-treated normal murine mammary gland cells

2016 ◽  
Vol 242 (2) ◽  
pp. 177-183 ◽  
Author(s):  
Dong Guo ◽  
Jia Guo ◽  
Xiang Li ◽  
Feng Guan
Keyword(s):  
Cell Adhesion ◽  
Mammary Gland ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Neural Cell Adhesion Molecule ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Gland Cells ◽  
Neural Cell Adhesion ◽  
Mammary Gland Cells

Glycosylation of certain proteins at the mammalian cell surface is an essential event in carcinogenesis. Sialylation, one type of glycosylation, can act on multiple cell-behaviors, such as migration, growth, and malignant invasion. Two polysialyltransferases, ST8Sia II (STX) and ST8Sia IV (PST), are responsible for synthesis of polysialic acid on neural cell adhesion molecule. We showed previously that STX and PST are oppositely expressed in normal murine mammary gland cells undergoing transforming growth factor-β-induced epithelial-mesenchymal transition. The molecular basis for regulation of STX and PST remained unclear. In the present study, we observed that transcription factor Pax3 upregulates STX expression, downregulates PST expression, and modulates upregulated expression of PSA, which attaches primarily to neural cell adhesion molecule to form PSA-NCAM. Overexpression of Pax3 in normal murine mammary gland cells transformed the expression of epithelial-mesenchymal transition markers E-cadherin and N-cadherin, and significantly promoted cell migration, but had no effect on cell proliferation.

scholarly journals Expression of Grainyhead-like 2 in the Process of Ductal Development of Mouse Mammary Gland

2021 ◽  
pp. 002215542110137
Author(s):  
Shinya Matsuoka ◽  
Hiroyoshi Suzuki ◽  
Chieko Kato ◽  
Mai Kamikawa-Tokai ◽  
Akihiro Kamikawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Mammary Gland ◽  
Epithelial Mesenchymal Transition ◽  
Combined Treatment ◽  
Myoepithelial Cells ◽  
Mouse Mammary Gland ◽  
Mesenchymal Transition ◽  
Ovariectomized Mice ◽  
Ductal Development

Grainyhead-like 2 (Grhl2) is a transcription factor regulating cell adhesion genes. Grhl2 acts as an epithelial–mesenchymal transition suppressor, and it is a proto-oncogene involved in estrogen-stimulated breast cancer proliferation. However, its expression during ovarian hormone–dependent mammary ductal development remains obscure. We here examined Grhl2 expression in the mammary gland of normal and steroid-replaced ovariectomized mice. Grhl2 protein signals were detected in both the mammary luminal epithelial and myoepithelial nuclei. The ratio and density of Grhl2-positive nuclei increased after the onset of puberty and progressed with age, whereas Grhl2-negative epithelial cells were detected in mature ducts. Claudin 3, claudin 4, claudin 7, and E-cadherin gene expression in the mammary gland was upregulated, and their expression was highly correlated with Grhl2 gene expression. Furthermore, Grhl2 mRNA expression and ductal lumen width were significantly increased by the combined treatment of estrogen and progesterone compared with estrogen alone. These results suggest that Grhl2 expressed in the luminal epithelial and myoepithelial cells from the early phase of ductal development, controlling the expression of cell adhesion molecules to establish functional ducts:

scholarly journals Roles for E-cadherin cell surface regulation in cancer

2016 ◽  
Vol 27 (21) ◽  
pp. 3233-3244 ◽  
Author(s):  
Yuliya I. Petrova ◽  
Leslayann Schecterson ◽  
Barry M. Gumbiner
Keyword(s):  
Mammary Gland ◽  
Cell Surface ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Diffuse Gastric Cancer ◽  
Missense Mutations ◽  
Mesenchymal Transition ◽  
Inside Out ◽  
E Cadherin

The loss of E-cadherin expression in association with the epithelial–mesenchymal transition (EMT) occurs frequently during tumor metastasis. However, metastases often retain E-cadherin expression, an EMT is not required for metastasis, and metastases can arise from clusters of tumor cells. We demonstrate that the regulation of the adhesive activity of E-cadherin present at the cell surface by an inside-out signaling mechanism is important in cancer. First, we find that the metastasis of an E-cadherin–expressing mammary cell line from the mammary gland to the lung depends on reduced E-cadherin adhesive function. An activating monoclonal antibody to E-cadherin that induces a high adhesive state significantly reduced the number of cells metastasized to the lung without affecting the growth in size of the primary tumor in the mammary gland. Second, we find that many cancer-associated germline missense mutations in the E-cadherin gene in patients with hereditary diffuse gastric cancer selectively affect the mechanism of inside-out cell surface regulation without inhibiting basic E-cadherin adhesion function. This suggests that genetic deficits in E-cadherin cell surface regulation contribute to cancer progression. Analysis of these mutations also provides insights into the molecular mechanisms underlying cadherin regulation at the cell surface.

scholarly journals Sox4 Regulates the Sensitivity of Canine Mammary Gland Tumor Cells to Cisplatin via the Wnt/β-catenin Signaling Pathway

2021 ◽  
Author(s):  
Mengxin Hu ◽  
Siqi Huang ◽  
Enshuang Xu ◽  
Danning Tong ◽  
Shengzi Jin ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Cell Line ◽  
Signaling Pathway ◽  
Cisplatin Resistance ◽  
Epithelial Mesenchymal Transition ◽  
Mammary Gland Tumor ◽  
Gland Tumor ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Canine Mammary Gland

Abstract Background: The development of cisplatin resistance is one of the major causes of breast cancer treatment failure, and is associated with changes in Sox4 gene expression. In this study, a cisplatin-resistant cell line, CHMpCIS, was constructed from the cell line CHMp, which was isolated from the primary lesion of a malignant canine mammary gland tumor (CMGT). Sox4 expression was evaluated to assess its roles in cisplatin sensitivity, proliferation and apoptosis, epithelial-mesenchymal transition (EMT), cancer stem cell (CSC) features, and activation of the Wnt/β-catenin signaling pathway in CMGT cells.Results: CHMpCIS Cells exhibited changes in morphology, slower proliferation, and greater anti-apoptotic ability, EMT and CSC features, and the Wnt/β-catenin pathway was activated in CHMpCIS cells. In CMGT tissues, Sox4 expression was elevated. In CHMpCIS cells, silencing Sox4 inhibited cisplatin resistance, EMT and CSC features, and Wnt/β-catenin signaling activation. Then activating the Wnt/β-catenin signaling pathway increased Sox4 expression levels.Conclusions: Silencing Sox4 inhibited the above-mentioned cancer cell characteristics in CHMpCIS cells compared with CHMp cells. In addition, activating the Wnt/β-catenin signaling pathway increased Sox4 expression levels, as part of a positive feedback loop. These findings may provide new targets and therapeutic strategies for the clinical treatment of CMGT as well as a reference for human mammary gland tumor (HMGT) research.

Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-Cripto-1 transgenic mice

2004 ◽  
Vol 201 (2) ◽  
pp. 266-276 ◽  
Author(s):  
Luigi Strizzi ◽  
Caterina Bianco ◽  
Nicola Normanno ◽  
Masaharu Seno ◽  
Christian Wechselberger ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Transgenic Mice ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition
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