TGF-β1-activated cancer-associated fibroblasts promote breast cancer invasion, metastasis and epithelial-mesenchymal transition by autophagy or overexpression of FAP-α

2021 ◽  
pp. 114527
Author(s):  
Minli Huang ◽  
Mengru Fu ◽  
Jia Wang ◽  
Chunhua Xia ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Invasion ◽  
Cancer Associated Fibroblasts ◽  
Mesenchymal Transition ◽  
Breast Cancer Invasion ◽  
Tgf Β1 ◽  
Promote Breast Cancer

scholarly journals MicroRNAs regulate the epithelial–mesenchymal transition and influence breast cancer invasion and metastasis

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769168 ◽  
Author(s):  
Min Zhao ◽  
Lin Ang ◽  
Jin Huang ◽  
Jin Wang
Keyword(s):  
Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Invasion ◽  
Invasion And Metastasis ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Rna Molecules ◽  
Breast Cancer Invasion ◽  
Proliferation And Apoptosis ◽  
Post Transcriptional Regulation

MicroRNAs are small RNA molecules that play a major role in the post-transcriptional regulation of genes and influence the development, differentiation, proliferation, and apoptosis of cells and the development and progression of tumors. The epithelial–mesenchymal transition is a process by which epithelial cells morphologically transform into cells with a mesenchymal phenotype. The epithelial–mesenchymal transition plays a highly important role in tumor invasion and metastasis. Increasing evidence indicates that microRNAs are tightly associated with epithelial–mesenchymal transition regulation in tumor cells. In breast cancer, various microRNA molecules have been identified as epithelial–mesenchymal transition inducers or inhibitors, which, through different mechanisms and signaling pathways, participate in the regulation of breast cancer invasion and metastasis among various biological behaviors. The epithelial–mesenchymal transition–related microRNAs in breast cancer provide valuable molecules for researching cell invasion and metastasis, and they also provide candidate targets that may be significant for the targeted therapy of breast cancer.

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 Cooperativity between stromal cytokines drives the invasive migration of human breast cancer cells

2019 ◽  
Vol 374 (1779) ◽  
pp. 20180231 ◽  
Author(s):  
Yair Elisha ◽  
Yael Sagi ◽  
Georg Klein ◽  
Ravid Straussman ◽  
Benjamin Geiger
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cross Talk ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Ex Vivo ◽  
Cancer Invasion ◽  
Stromal Fibroblast ◽  
Mesenchymal Transition ◽  
Interdisciplinary Approaches

The cross-talk between cancer cells and the stromal microenvironment plays a key role in regulating cancer invasion. Here, we employed an ex vivo invasion model system for exploring the regulation of breast cancer cells infiltration into a variety of stromal fibroblast monolayers. Our results revealed considerable variability in the stromal induction of invasiveness, with some lines promoting and others blocking invasion. It was shown that conditioned medium (CM), derived from invasion-promoting fibroblasts, can induce epithelial–mesenchymal transition-like process in the cancer cells, and trigger their infiltration into a monolayer of invasion-blocking fibroblasts. To identify the specific invasion-promoting molecules, we analysed the cytokines in stimulatory CM, screened a library of purified cytokines for invasion-promoting activity and tested the effect of specific inhibitors of selected cytokine receptors on the CM-induced invasion. Taken together, these experiments indicated that the invasiveness of BT-474 is induced by the combined action of IL1 and IL6 and that IL1 can induce IL6 secretion by invasion-blocking fibroblasts, thereby triggering cancer cell invasion into the stroma. This unexpected observation suggests that stromal regulation of cancer invasion may involve not only cross-talk between stromal and cancer cells, but also cooperation between different stromal subpopulations. This article is part of a discussion meeting issue ‘Forces in cancer: interdisciplinary approaches in tumour mechanobiology’.

scholarly journals Galectin-1 From Cancer-Associated Fibroblasts Promotes the Invasion and Metastasis of Gastric Cancer Through TGF-β1-Induced Epithelial-Mesenchymal Transition

2021 ◽  
Author(s):  
xiaolan you ◽  
Jian Wu ◽  
Xiaojun Zhao ◽  
Xingyu Jiang ◽  
Wenxuan Tao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Invasion ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Associated Fibroblasts ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration ◽  
Tgf Β1

Abstract Background The gastric cancer (GC) microenvironment has important effects on biological behaviors, such as tumor cell invasion and metastasis. However, the mechanism by which the GC microenvironment promotes GC cell invasion and metastasis is unknown. The present study aimed to clarify the effects and mechanism of galectin-1 (GAL-1, encoded by LGALS1) on GC invasion and metastasis in the GC microenvironment.Methods The expression of GAL-1/ LGALS1 was determined using western blotting, immunohistochemistry, and quantitative real-time reverse transcription PCR in GC tissues. Besides, methods including stable transfection, Matrigel invasion and migration assays, and wound-healing assays in vitro; and metastasis assays in vivo, were also conducted.Results GAL-1 from cancer-associated fibroblasts (CAFs) induced the epithelial‑mesenchymal transition (EMT) of GC cells though the transforming growth factor beta (TGF-β1)/ Sma- and mad-related protein (Smad) pathway, and affected the prognosis of patients with GC. The level of GAL-1 was high in CAFs, and treating MGC-803 and SGC -7901 cell line with the conditioned medium from CAFs promoted their invasion and metastasis abilities. Overexpression of LGALS1 promoted the expression of TGF-β1 and induced EMT of GC cell lines. A TGF-β1 antagonist inhibited the invasion and migration of GC cells. In vivo, overexpression of LGALS1 promoted GC growth and metastasis, and the TGF-β1 antagonist dramatically reversed these events. Conclusions These findings suggested that high expression of GAL-1 in the GC microenvironment predicts a poor prognosis in patients with GC by promoting the migration and invasion of GC cells via EMT through the TGF-β1/Smad signaling pathway. The results might provide new therapeutic targets to treat GC.

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