Loss of TMEM126A promotes extracellular matrix remodeling, epithelial-to-mesenchymal transition, and breast cancer metastasis by regulating mitochondrial retrograde signaling

2019 ◽  
Vol 440-441 ◽  
pp. 189-201 ◽  
Author(s):  
He-Fen Sun ◽  
Xue-li Yang ◽  
Yang Zhao ◽  
Qi Tian ◽  
Meng-Ting Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Breast Cancer Metastasis ◽  
Retrograde Signaling ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Mesenchymal Transition ◽  
Mitochondrial Retrograde Signaling

scholarly journals Tracking Extracellular Matrix Remodeling in Lungs Induced by Breast Cancer Metastasis. Fourier Transform Infrared Spectroscopic Studies

Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 236 ◽  
Author(s):  
Karolina Chrabaszcz ◽  
Katarzyna Kaminska ◽  
Karolina Augustyniak ◽  
Monika Kujdowicz ◽  
Marta Smeda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Fourier Transform ◽  
Cancer Metastasis ◽  
Fourier Transform Infrared ◽  
Muscle Cells ◽  
Breast Cancer Metastasis ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Large Area

This work focused on a detailed assessment of lung tissue affected by metastasis of breast cancer. We used large-area chemical scanning implemented in Fourier transform infrared (FTIR) spectroscopic imaging supported with classical histological and morphological characterization. For the first time, we differentiated and defined biochemical changes due to metastasis observed in the lung parenchyma, atelectasis, fibrous, and muscle cells, as well as bronchi ciliate cells, in a qualitative and semi-quantitative manner based on spectral features. The results suggested that systematic extracellular matrix remodeling with the progress of the metastasis process evoked a decrease in the fraction of the total protein in atelectasis, fibrous, and muscle cells, as well as an increase of fibrillar proteins in the parenchyma. We also detected alterations in the secondary conformations of proteins in parenchyma and atelectasis and changes in the level of hydroxyproline residues and carbohydrate moieties in the parenchyma. The results indicate the usability of FTIR spectroscopy as a tool for the detection of extracellular matrix remodeling, thereby enabling the prediction of pre-metastatic niche formation.

Role of E2F3 and shugoshin I in epithelial-to-mesenchymal transition and cell invasion in breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13100-e13100
Author(s):  
Shirley Jusino ◽  
Srikumar P. Chellappan ◽  
Harold I. Saavedra
Keyword(s):  
Breast Cancer ◽  
Cell Invasion ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Cellular Proliferation ◽  
Protein Localization ◽  
Breast Cancer Metastasis ◽  
Mrna Levels ◽  
Mesenchymal Transition

e13100 Background: Triple-negative breast cancer (TNBC) is the most aggressive and poorly prognostic breast cancer subtype, yet there are currently no biological therapies against this subtype. Our laboratory is finding the sources of novel biological targets in TNBC by studying the E2F transcription factors, which are essential for cellular proliferation and maintenance of genomic stability. While the deregulated Rb/E2F pathway signals the epithelial-to-mesenchymal transition (EMT), the underlining mechanism of how E2Fs drive EMT in TNBC remains unknown. We recently published that the E2F transcriptional activators (E2Fs) are overexpressed in the vast majority of TNBC and that their overexpression upregulates mitotic kinases such as TTK, which we have shown to induce EMT and invasion in TNBC cells. We also demonstrated that the E2Fs maintain genomic integrity in part through Shugoshin I (SGO1), which normally controls chromosome cohesion; however, the role of SGO1 in EMT in breast cancer is unknown. Our hypothesis is that E2F3 and SGO1 are highly expressed in TNBC and that their overexpression modulates EMT genes, thus promoting cell invasion. Methods: To test our hypothesis, we conducted siRNA transfection to knockdown E2F3 and SGO1 in MDA-MB-231 and Hs578t, which are TNBC cells. After 48 hours, we evaluated mRNA levels of EMT-related genes after E2F3 or SGO1 depletion using RT-PCR analysis. We also evaluated the effects of SGO1 depletion in protein localization by immunofluorescence. Furthermore, we evaluated the invasive behavior of MDA-MB-231 and Hs578t cells after SGO1 depletion using a Boyden Chamber Assay. Results: Our results demonstrate that E2F3 and SGO1 depletion decrease MMP3 mRNA levels. Moreover, E2F3 and SGO1 depletion restore E-cadherin expression and localization. Furthermore, E2F3 and SGO1 depletion significantly reduce cell invasion in MDA-MB-231 and Hs578t cells. Conclusions: Our results suggest that SGO1 is a promising drug target for breast cancer metastasis since EMT and invasion are essential early steps in breast cancer metastasis and E2F3 is presently undruggable.

scholarly journals Long Non-Coding RNA: Dual Effects on Breast Cancer Metastasis and Clinical Applications

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1802 ◽  
Author(s):  
Qi-Yuan Huang ◽  
Guo-Feng Liu ◽  
Xian-Ling Qian ◽  
Li-Bo Tang ◽  
Qing-Yun Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Distant Metastasis ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Therapy Resistance ◽  
Breast Cancer Metastasis ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Regulatory Effects ◽  
Long Non Coding Rna

As a highly heterogeneous malignancy, breast cancer (BC) has become the most significant threat to female health. Distant metastasis and therapy resistance of BC are responsible for most of the cases of mortality and recurrence. Distant metastasis relies on an array of processes, such as cell proliferation, epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), and angiogenesis. Long non-coding RNA (lncRNA) refers to a class of non-coding RNA with a length of over 200 nucleotides. Currently, a rising number of studies have managed to investigate the association between BC and lncRNA. In this study, we summarized how lncRNA has dual effects in BC metastasis by regulating invasion, migration, and distant metastasis of BC cells. We also emphasize that lncRNA has crucial regulatory effects in the stemness and angiogenesis of BC. Clinically, some lncRNAs can regulate chemotherapy sensitivity in BC patients and may function as novel biomarkers to diagnose or predict prognosis for BC patients. The exact impact on clinical relevance deserves further study. This review can be an approach to understanding the dual effects of lncRNAs in BC, thereby linking lncRNAs to quasi-personalized treatment in the future.

scholarly journals Exosomal microRNAs: Pleiotropic Impacts on Breast Cancer Metastasis and Their Clinical Perspectives

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 307
Author(s):  
Li-Bo Tang ◽  
Shu-Xin Ma ◽  
Zhuo-Hui Chen ◽  
Qi-Yuan Huang ◽  
Long-Yuan Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Sensitivity ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Breast Cancer Metastasis ◽  
Mesenchymal Transition ◽  
Diagnosis And Prognosis ◽  
Pathological Conditions ◽  
Mesenchymal To Epithelial Transition ◽  
Exosomal Mirnas

As a major threat factor for female health, breast cancer (BC) has garnered a lot of attention for its malignancy and diverse molecules participating in its carcinogenesis process. Among these complex carcinogenesis processes, cell proliferation, epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), and angiogenesis are the major causes for the occurrence of metastasis and chemoresistance which account for cancer malignancy. MicroRNAs packaged and secreted in exosomes are termed “exosomal microRNAs (miRNAs)”. Nowadays, more researches have uncovered the roles of exosomal miRNAs played in BC metastasis. In this review, we recapitulated the dual actions of exosomal miRNAs exerted in the aggressiveness of BC by influencing migration, invasion, and distant metastasis. Next, we presented how exosomal miRNAs modify angiogenesis and stemness maintenance. Clinically, several exosomal miRNAs can govern the transformation between drug sensitivity and chemoresistance. Since the balance of the number and type of exosomal miRNAs is disturbed in pathological conditions, they are able to serve as instructive biomarkers for BC diagnosis and prognosis. More efforts are needed to connect the theoretical studies and clinical traits together. This review provides an outline of the pleiotropic impacts of exosomal miRNAs on BC metastasis and their clinical implications, paving the way for future personalized drugs.

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