Msi1 promotes breast cancer metastasis by regulating invadopodia-mediated extracellular matrix degradation via the Timp3–Mmp9 pathway

AbstractDuring breast cancer metastasis, cancer cell invasion is driven by actin-rich protrusions called invadopodia, which mediate the extracellular matrix degradation required for the success of the invasive cascade. In this study, we demonstrated that TC10, a member of a Cdc42 subfamily of p21 small GTPases, regulates the membrane type 1 matrix metalloproteinase (MT1-MMP)-driven extracellular matrix degradation at invadopodia. We show that TC10 is required for the plasma membrane surface exposure of MT1-MMP at invadopodia. By utilizing our new Förster resonance energy transfer (FRET) biosensor, we demonstrated the p190RhoGAP-dependent regulation of spatiotemporal TC10 activity at invadopodia. We identified a pathway that regulates TC10 activity and function at invadopodia through the activation of p190RhoGAP and the downstream interacting effector Exo70 at the invadopodia sites. Our findings reveal the role of a previously unknown regulator of vesicular fusion at invadopodia, TC10, on the invasive potential of breast cancer cells during invasion and metastasis.

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

Molecules ◽

10.3390/molecules25010236 ◽

2020 ◽

Vol 25 (1) ◽

pp. 236 ◽

Cited By ~ 3

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.

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TLR4 blockade using TAK-242 suppresses ovarian and breast cancer cells invasion through the inhibition of extracellular matrix degradation and epithelial-mesenchymal transition

European Journal of Pharmacology ◽

10.1016/j.ejphar.2019.03.046 ◽

2019 ◽

Vol 853 ◽

pp. 256-263 ◽

Cited By ~ 20

Author(s):

Zahra Zandi ◽

Bahareh Kashani ◽

Ensieh M. Poursani ◽

Davood Bashash ◽

Majid Kabuli ◽

...

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Matrix Degradation ◽

Mesenchymal Transition ◽

Extracellular Matrix Degradation

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Paving the way for metastasis: microRNA set dysregulation in breast cancer cells can contribute to the extracellular matrix degradation and remodeling

The Breast ◽

10.1016/s0960-9776(19)30153-5 ◽

2019 ◽

Vol 44 ◽

pp. S32-S33

Author(s):

V. Halytskiy

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Matrix Degradation ◽

Extracellular Matrix Degradation ◽

The Way

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Compressive Stress Enhances Invasive Phenotype of Breast Cancer Cells via Piezo1 Activation

10.21203/rs.2.18102/v1 ◽

2019 ◽

Author(s):

Mingzhi Luo ◽

Kenneth KY Ho ◽

Zhaowen Tong ◽

Linhong Deng ◽

Allen Liu

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Compressive Stress ◽

Breast Cancer Cells ◽

Cancer Metastasis ◽

Calcium Influx ◽

Breast Cancer Metastasis ◽

Matrix Degradation ◽

Apical Side ◽

Actin Protrusions

Abstract Uncontrolled growth in solid tumor generates compressive stress that drives cancer cells into invasive phenotypes, but little is known about how such stress affects the invasion and matrix degradation of cancer cells and the underlying mechanisms. Here we show that compressive stress enhanced invasion and matrix degradation of breast cancer cells. We further identified Piezo1 as the putative mechanosensitive cellular component that transmits compressive stress to induce calcium influx, which in turn activate Src/ERK signaling. Interestingly, we observed actin protrusions with matrix degradation ability on the apical side of the cells. Furthermore, we demonstrate that Piezo1 channels were partially localized in caveolae, and reduction of caveolin-1 expression or disruption of caveolae with methyl-β-cyclodextrin led to not only reduced Piezo1 expression but also attenuation of the invasive phenotypes promoted by compressive stress. Taken together, our data indicate that mechanical compressive stress activates Piezo1 channels to mediate enhanced cancer cell invasion and matrix degradation that may be a critical mechanotransduction pathway during, and potentially a novel therapeutic target for, breast cancer metastasis.

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Compression enhances invasive phenotype and matrix degradation of breast Cancer cells via Piezo1 activation

BMC Molecular and Cell Biology ◽

10.1186/s12860-021-00401-6 ◽

2022 ◽

Vol 23 (1) ◽

Author(s):

Mingzhi Luo ◽

Grace Cai ◽

Kenneth K. Y. Ho ◽

Kang Wen ◽

Zhaowen Tong ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cancer Metastasis ◽

Calcium Influx ◽

Cholesterol Content ◽

Breast Cancer Metastasis ◽

Matrix Degradation ◽

Mechanical Compression ◽

Invasive Phenotype

Abstract Background Uncontrolled growth in solid breast cancer generates mechanical compression that may drive the cancer cells into a more invasive phenotype, but little is known about how such compression affects the key events and corresponding regulatory mechanisms associated with invasion of breast cancer cells including cellular behaviors and matrix degradation. Results Here we show that compression enhanced invasion and matrix degradation of breast cancer cells. We also identified Piezo1 as the putative mechanosensitive cellular component that transmitted compression to not only enhance the invasive phenotype, but also induce calcium influx and downstream Src signaling. Furthermore, we demonstrated that Piezo1 was mainly localized in caveolae, and both Piezo1 expression and compression-enhanced invasive phenotype of the breast cancer cells were reduced when caveolar integrity was compromised by either knocking down caveolin1 expression or depleting cholesterol content. Conclusions Taken together, our data indicate that mechanical compression activates Piezo1 channels to mediate enhanced breast cancer cell invasion, which involves both cellular events and matrix degradation. This may be a critical mechanotransduction pathway during breast cancer metastasis, and thus potentially a novel therapeutic target for the disease.

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Faciogenital Dysplasia Protein Fgd1 Regulates Invadopodia Biogenesis and Extracellular Matrix Degradation and Is Up-regulated in Prostate and Breast Cancer

Cancer Research ◽

10.1158/0008-5472.can-08-1980 ◽

2009 ◽

Vol 69 (3) ◽

pp. 747-752 ◽

Cited By ~ 56

Author(s):

Inmaculada Ayala ◽

Giada Giacchetti ◽

Giusi Caldieri ◽

Francesca Attanasio ◽

Stefania Mariggiò ◽

...

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Matrix Degradation ◽

Extracellular Matrix Degradation ◽

Faciogenital Dysplasia

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Inhibitory Effects of PC-SPESII Herbal Extract on Human Breast Cancer Metastasis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/894386 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Xiu-Feng Wang ◽

Jia Du ◽

Tian-Ling Zhang ◽

Qian-Mei Zhou ◽

Yi-Yu Lu ◽

...

Keyword(s):

Breast Cancer ◽

Human Breast Cancer ◽

Cancer Metastasis ◽

Proteolytic Enzymes ◽

Breast Cancer Metastasis ◽

Herbal Extract ◽

Dependent Manner ◽

Matrix Degradation ◽

Human Breast

Cancer metastasis is refractory to most forms of chemotherapy. Conventional and alternative drugs, such as Chinese herbal remedies, have been developed to target metastatic cancer cells. In this study, we investigated the effects of PC-SPESII, an herbal formulation, on the migration, invasion, and metastasis of an experimental human breast cancer cell linein vivoandin vitro. PC-SPESII suppressed pulmonary metastasis and tumor growth of MDA-MB-231 human breast cancer xenografts without affecting body weight, liver function, and kidney function. PC-SPESII also inhibited MDA-MB-231 cell migration and invasionin vitroin a dose-dependent manner. Based on ELISA analysis, secretion of MMP-2 and MMP-9, proteins associated with extracellular matrix degradation, was reduced in response to PC-SPESII treatment. Western blot analysis of whole-cell extracts revealed that the levels of proteolytic proteins associated with matrix and base membrane degradation (MMP-2, MMP-9, and uPA) were decreased and the levels of their endogenous inhibitors (TIMP1 and TIMP2) were increased. Moreover, the p38MAPK and SAPK/JNK signaling pathway, which stimulates proteolytic enzymes and matrix degradation, was inhibited by PC-PSESII. Remarkably, cotreatment with PC-PSESII and p38MAPK or SAPK/JNK inhibitors magnified the antimetastatic phenotype. Our results indicate that PC-PSESII impairs human breast cancer metastasis by regulating proteolytic enzymes and matrix dynamics through the p38MAPK and SAPK/JNK pathway.

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