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The interplay between extracellular matrix remodelling and kinase signalling in cancer progression and metastasis.

ABSTRACT: The extracellular matrix (ECM) is a master regulator of cellular phenotype and behaviour. It plays a crucial role in both normal tissue homeostasis and complex diseases such as cancer. The interplay between the intrinsic factors of cancer cells themselves, including their genotype and signalling networks; and the extrinsic factors of the tumour stroma, such as the ECM and ECM remodelling; together determine the fate and behaviour of cancer cells. As a consequence, tumour progression, metastatic spread and response to therapy are ultimately controlled by ECM-driven fine-tuning of intracellular kinase signalling. The ability to target and uncouple this interaction presents an emerging and promising potential in the treatment of cancer.

SUBMITTER: Skhinas JN

PROVIDER: S-EPMC6363022 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The interplay between extracellular matrix remodelling and kinase signalling in cancer progression and metastasis.

Skhinas Joanna N JN Cox Thomas R TR

Cell adhesion & migration 20171229 6

The extracellular matrix (ECM) is a master regulator of cellular phenotype and behaviour. It plays a crucial role in both normal tissue homeostasis and complex diseases such as cancer. The interplay between the intrinsic factors of cancer cells themselves, including their genotype and signalling networks; and the extrinsic factors of the tumour stroma, such as the ECM and ECM remodelling; together determine the fate and behaviour of cancer cells. As a consequence, tumour progression, metastatic ...[more]

PMID: 29168660

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Project description:BACKGROUND: Cancer metastasis is the main contributor to breast cancer fatalities as women with the metastatic disease have poorer survival outcomes than women with localised breast cancers. There is an urgent need to develop appropriate prognostic methods to stratify patients based on the propensities of their cancers to metastasise. The insulin-like growth factor (IGF)-I: IGF binding protein (IGFBP):vitronectin complexes have been shown to stimulate changes in gene expression favouring increased breast cancer cell survival and a migratory phenotype. We therefore investigated the prognostic potential of these IGF- and extracellular matrix (ECM) interaction-induced proteins in the early identification of breast cancers with a propensity to metastasise using patient-derived tissue microarrays. METHODS: Semiquantitative immunohistochemistry analyses were performed to compare the extracellular and subcellular distribution of IGF- and ECM-induced signalling proteins among matched normal, primary cancer and metastatic cancer formalin-fixed paraffin-embedded breast tissue samples. RESULTS: The IGF- and ECM-induced signalling proteins were differentially expressed between subcellular and extracellular localisations. Vitronectin and IGFBP-5 immunoreactivity was lower while ?1 integrin immunoreactivity was higher in the stroma surrounding metastatic cancer tissues, as compared to normal breast and primary cancer stromal tissues. Similarly, immunoreactive stratifin was found to be increased in the stroma of primary as well as metastatic breast tissues. Immunoreactive fibronectin and ?1 integrin was found to be highly expressed at the leading edge of tumours. Based on the immunoreactivity it was apparent that the cell signalling proteins AKT1 and ERK1/2 shuffled from the nucleus to the cytoplasm with tumour progression. CONCLUSION: This is the first in-depth, compartmentalised analysis of the distribution of IGF- and ECM-induced signalling proteins in metastatic breast cancers. This study has provided insights into the changing pattern of cellular localisation and expression of IGF- and ECM-induced signalling proteins in different stages of breast cancer. The differential distribution of these biomarkers could provide important prognostic and predictive indicators that may assist the clinical management of breast disease, namely in the early identification of cancers with a propensity to metastasise, and/or recur following adjuvant therapy.

Dataset Information

The interplay between extracellular matrix remodelling and kinase signalling in cancer progression and metastasis.

Publications

The interplay between extracellular matrix remodelling and kinase signalling in cancer progression and metastasis.

Similar Datasets

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