Fibroblastic FAK controls pancreatic cancer metastasis by enhancing extracellular matrix remodeling

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

Cancer Letters ◽

10.1016/j.canlet.2018.10.018 ◽

2019 ◽

Vol 440-441 ◽

pp. 189-201 ◽

Cited By ~ 5

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

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Lysyl Oxidase, Extracellular Matrix Remodeling and Cancer Metastasis

Cancer Microenvironment ◽

10.1007/s12307-012-0105-z ◽

2012 ◽

Vol 5 (3) ◽

pp. 261-273 ◽

Cited By ~ 98

Author(s):

Qian Xiao ◽

Gaoxiang Ge

Keyword(s):

Extracellular Matrix ◽

Cancer Metastasis ◽

Lysyl Oxidase ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling

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YAP1 is an independent prognostic marker in pancreatic cancer and associated with extracellular matrix remodeling

Journal of Translational Medicine ◽

10.1186/s12967-020-02254-7 ◽

2020 ◽

Vol 18 (1) ◽

Cited By ~ 6

Author(s):

Qimin Zhou ◽

Monika Bauden ◽

Roland Andersson ◽

Dingyuan Hu ◽

György Marko-Varga ◽

...

Keyword(s):

Pancreatic Cancer ◽

Extracellular Matrix ◽

Overall Survival ◽

Cancer Patients ◽

Extracellular Matrix Remodeling ◽

Cancer Tissue ◽

Matrix Remodeling ◽

Expression Data ◽

Pancreatic Cancer Tissue ◽

Immunohistochemistry Analysis

Abstract Background Pancreatic cancer is a major cause of cancer-related mortality. The identification of effective biomarkers is essential in order to improve management of the disease. Yes-associated protein 1 (YAP1) is a downstream effector of the Hippo pathway, a signal transduction system implicated in tissue repair and regeneration, as well as tumorigenesis. Here we evaluate the biomarker potential of YAP1 in pancreatic cancer tissue. Methods YAP1 was selected as a possible biomarker for pancreatic cancer from global protein sequencing of fresh frozen pancreatic cancer tissue samples and normal pancreas controls. The prognostic utility of YAP1 was evaluated using mRNA expression data from 176 pancreatic cancer patients in The Cancer Genome Atlas (TCGA), as well as protein expression data from immunohistochemistry analysis of a local tissue microarray (TMA) cohort comprising 140 pancreatic cancer patients. Ingenuity Pathway Analysis was applied to outline the interaction network for YAP1 in connection to the pancreatic tumor microenvironment. The expression of YAP1 target gene products was evaluated after treatment of the pancreatic cancer cell line Panc-1 with three substances interrupting YAP–TEAD interaction, including Super-TDU, Verteporfin and CA3. Results Mass spectrometry based proteomics showed that YAP1 is the top upregulated protein in pancreatic cancer tissue when compared to normal controls (log2 fold change 6.4; p = 5E−06). Prognostic analysis of YAP1 demonstrated a significant correlation between mRNA expression level data and reduced overall survival (p = 0.001). In addition, TMA and immunohistochemistry analysis suggested that YAP1 protein expression is an independent predictor of poor overall survival [hazard ratio (HR) 1.870, 95% confidence interval (CI) 1.224–2.855, p = 0.004], as well as reduced disease-free survival (HR 1.950, 95% CI 1.299–2.927, p = 0.001). Bioinformatic analyses coupled with in vitro assays indicated that YAP1 is involved in the transcriptional control of target genes, associated with extracellular matrix remodeling, which could be modified by selected substances disrupting the YAP1-TEAD interaction. Conclusions Our findings indicate that YAP1 is an important prognostic biomarker for pancreatic cancer and may play a regulatory role in the remodeling of the extracellular matrix.

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Faculty Opinions recommendation of Sweet, yet underappreciated: Proteoglycans and extracellular matrix remodeling in heart disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732498270.793541733 ◽

2018 ◽

Author(s):

Nikos Karamanos

Keyword(s):

Extracellular Matrix ◽

Heart Disease ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling

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The Dynamic Interaction between Extracellular Matrix Remodeling and Breast Tumor Progression

Cells ◽

10.3390/cells10051046 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1046

Author(s):

Jorge Martinez ◽

Patricio C. Smith

Keyword(s):

Extracellular Matrix ◽

Type I Collagen ◽

Cell Metabolism ◽

Breast Tumors ◽

Extracellular Matrix Remodeling ◽

Type I ◽

Matrix Remodeling ◽

Desmoplastic Reaction ◽

The Impact

Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this type of lesion, a property that allows its palpation and early detection. Fibrillar type I collagen is a major component of tumor desmoplasia and its accumulation is causally linked to tumor cell survival and metastasis. For many years, the desmoplastic phenomenon was considered to be a reaction and response of the host tissue against tumor cells and, accordingly, designated as “desmoplastic reaction”. This notion has been challenged in the last decades when desmoplastic tissue was detected in breast tissue in the absence of tumor. This finding suggests that desmoplasia is a preexisting condition that stimulates the development of a malignant phenotype. With this perspective, in the present review, we analyze the role of extracellular matrix remodeling in the development of the desmoplastic response. Importantly, during the discussion, we also analyze the impact of obesity and cell metabolism as critical drivers of tissue remodeling during the development of desmoplasia. New knowledge derived from the dynamic remodeling of the extracellular matrix may lead to novel targets of interest for early diagnosis or therapy in the context of breast tumors.

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