Extracellular matrix protein 1 recruits moesin to facilitate invadopodia formation and breast cancer metastasis

AbstractBackgroundThe extracellular matrix (ECM) is a fundamental component of multicellular organisms that orchestrates developmental processes and controls cell and tissue organization. We previously identified the novel ECM protein SNED1 as a promoter of breast cancer metastasis and showed that its level of expression negatively correlated with survival of breast cancer patients. Here we sought to identify the roles of SNED1 during murine development and in physiology.ResultsWe generated two novel Sned1 knockout mouse strains and showed that Sned1 is essential since homozygous ablation of the gene led to ~67% early neonatal lethality. Phenotypic analysis of the surviving knockout mice obtained revealed a role for SNED1 in the development of craniofacial and skeletal structures since Sned1 knockout resulted in growth defects, nasal cavity occlusion, and craniofacial malformations. Sned1 is widely expressed in embryos, notably in neural-crest derivatives. We further show here that mice with a neural-crest-cell-specific deletion of Sned1 survive, but display facial anomalies partly phenocopying the global knockout mice.ConclusionsOur results demonstrate requisite roles for SNED1 during development and neonatal survival. Importantly, the deletion of 2q37.3 in humans, a region that includes the SNED1 locus, has been associated with facial dysmorphism and short stature.

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The role of extracellular matrix protein 1 in human skin

Clinical and Experimental Dermatology ◽

10.1111/j.1365-2230.2004.01440.x ◽

2004 ◽

Vol 29 (1) ◽

pp. 52-56 ◽

Cited By ~ 58

Author(s):

I. Chan

Keyword(s):

Extracellular Matrix ◽

Human Skin ◽

Matrix Protein ◽

Extracellular Matrix Protein ◽

Extracellular Matrix Protein 1

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Characterization of the human extracellular matrix protein 1 gene on chromosome 1q21

Matrix Biology ◽

10.1016/s0945-053x(97)90017-2 ◽

1997 ◽

Vol 16 (5) ◽

pp. 289-292 ◽

Cited By ~ 27

Author(s):

Maureen R. Johnson ◽

Douglas J. Wilkin ◽

Hans L. Vos ◽

Rosa Isela Ortiz De Luna ◽

Anindya M. Dehejia ◽

...

Keyword(s):

Extracellular Matrix ◽

Matrix Protein ◽

Extracellular Matrix Protein ◽

Extracellular Matrix Protein 1 ◽

Chromosome 1Q21

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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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Epidermal growth factor‐containing fibulin‐like extracellular matrix protein 1 ( EFEMP 1) suppressed the growth of hepatocellular carcinoma cells by promoting Semaphorin 3B( SEMA 3B)

Cancer Medicine ◽

10.1002/cam4.2144 ◽

2019 ◽

Vol 8 (6) ◽

pp. 3152-3166 ◽

Cited By ~ 3

Author(s):

Jiangfeng Hu ◽

Bensong Duan ◽

Weiliang Jiang ◽

Sengwang Fu ◽

Hengjun Gao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Extracellular Matrix ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Matrix Protein ◽

Carcinoma Cells ◽

Extracellular Matrix Protein ◽

Hepatocellular Carcinoma Cells ◽

Extracellular Matrix Protein 1 ◽

Epidermal Growth

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003 Detection of serum autoantibodies to extracellular matrix protein 1 (ECM1) and relevant abnormal expression of hemidesmosomal antigens in lichen sclerosus

Journal of Investigative Dermatology ◽

10.1016/j.jid.2018.03.007 ◽

2018 ◽

Vol 138 (5) ◽

pp. S1

Author(s):

N. Utsunomiya ◽

N. Oyama ◽

T. Chino ◽

A. Utsunomiya ◽

L. Vu Huy ◽

...

Keyword(s):

Extracellular Matrix ◽

Matrix Protein ◽

Lichen Sclerosus ◽

Extracellular Matrix Protein ◽

Abnormal Expression ◽

Extracellular Matrix Protein 1

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Baicalein inhibits fibronectin-induced epithelial–mesenchymal transition by decreasing activation and upregulation of calpain-2

Cell Death and Disease ◽

10.1038/s41419-019-1572-7 ◽

2019 ◽

Vol 10 (5) ◽

Cited By ~ 4

Author(s):

Yan Chen ◽

Lin Chen ◽

Duanyang Hong ◽

Zongyue Chen ◽

Jingyu Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Cellular Response ◽

Matrix Protein ◽

Epithelial Mesenchymal Transition ◽

T Antigen ◽

Extracellular Matrix Protein ◽

Mesenchymal Transition ◽

Calpain 2 ◽

E Cadherin

AbstractThe extracellular matrix protein fibronectin (FN) facilitates tumorigenesis and the development of breast cancer. Inhibition of the FN-induced cellular response is a potential strategy for breast cancer treatment. In the present study, we investigated the effects of the flavonoid baicalein on FN-induced epithelial–mesenchymal transition (EMT) in MCF-10A breast epithelial cells and in a transgenic mouse MMTV-polyoma middle T antigen breast cancer model (MMTV-PyMT). Baicalein inhibited FN-induced migration, invasion, and F-actin remodeling. Baicalein also suppressed FN-induced downregulation of the epithelial markers E-cadherin and ZO-1 and upregulation of the mesenchymal markers N-cadherin, vimentin, and Snail. Further investigation revealed that calpain-2 was involved in baicalein suppression of FN-induced EMT. Baicalein significantly decreased FN-enhanced calpain-2 expression and activation by suppressing its plasma membrane localization, substrate cleavage, and degradation of its endogenous inhibitor calpastatin. Overexpression of calpain-2 in MCF-10A cells by gene transfection partially blocked the inhibitory effect of baicalein on FN-induced EMT changes. In addition, baicalein inhibited calpain-2 by decreasing FN-increased intracellular calcium ion levels and extracellular signal-regulated protein kinases activation. Baicalein significantly decreased tumor onset, growth, and pulmonary metastasis in a spontaneous breast cancer MMTV-PyMT mouse model. Baicalein also reduced the expression of FN, calpain-2, and vimentin, but increased E-cadherin expression in MMTV-PyMT mouse tumors. Overall, these results revealed that baicalein markedly inhibited FN-induced EMT by inhibiting calpain-2, thus providing novel insights into the pharmacological action and mechanism of baicalein. Baicalein may therefore possess therapeutic potential for the treatment of breast cancer though interfering with extracellular matrix–cancer cell interactions.

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