Collagen and fibronectin promote an aggressive cancer phenotype in breast cancer cells but drive autonomous gene expression patterns

Nolan, Joanne; Mahdi, Amira F.; Dunne, Colum P.; Kiely, Patrick A.

doi:10.1016/j.gene.2020.145024

Cited by 13 publications

(8 citation statements)

References 35 publications

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“…Increased expression of fibrillar collagen (e.g., type I and type III collagen) in BC may be associated with tumor invasion and aggressive tumor behavior. The relationship between changes in collagen production and BC progression may be functionally important (25)(26)(27).…”

Section: Collagensmentioning

confidence: 99%

Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer

Zhao

Zheng

et al. 2021

Front. Oncol.

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Increasing evidence shows that the extracellular matrix (ECM) is an important regulator of breast cancer (BC). The ECM comprises of highly variable and dynamic components. Compared with normal breast tissue under homeostasis, the ECM undergoes many changes in composition and organization during BC progression. Induced ECM proteins, including fibrinogen, fibronectin, hyaluronic acid, and matricellular proteins, have been identified as important components of BC metastatic cells in recent years. These proteins play major roles in BC progression, invasion, and metastasis. Importantly, several specific ECM molecules, receptors, and remodeling enzymes are involved in promoting resistance to therapeutic intervention. Additional analysis of these ECM proteins and their downstream signaling pathways may reveal promising therapeutic targets against BC. These potential drug targets may be combined with new nanoparticle technologies. This review summarizes recent advances in functional nanoparticles that target the ECM to treat BC. Accurate nanomaterials may offer a new approach to BC treatment.

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Section: Collagensmentioning

confidence: 99%

Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer

Zhao

Zheng

et al. 2021

Front. Oncol.

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“…Using immunoblot analysis we firstly investigated how the expression and regulation of Annexin A2 in breast cancer cells is affected by the presence of collagen-I. Collagen-I was chosen as it is the most abundant constituent of the ECM and is linked to breast cancer proliferation, migration and metastasis ( 7 , 9 , 11 , 48 ). We were interested to see that, in the presence of collagen-I, the phosphorylation of Annexin A2 at Tyr24 is dramatically increased, as illustrated in Figure 1A .…”

Section: Resultsmentioning

confidence: 99%

Collagen-I influences the post-translational regulation, binding partners and role of Annexin A2 in breast cancer progression

Mahdi,

Nolan,

O’Connor

et al. 2023

Front. Oncol.

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IntroductionThe extracellular matrix (ECM) has been heavily implicated in the development and progression of cancer. We have previously shown that Annexin A2 is integral in the migration and invasion of breast cancer cells and in the clinical progression of ER-negative breast cancer, processes which are highly influenced by the surrounding tumor microenvironment and ECM.MethodsWe investigated how modulations of the ECM may affect the role of Annexin A2 in MDA-MB-231 breast cancer cells using western blotting, immunofluorescent confocal microscopy and immuno-precipitation mass spectrometry techniques.ResultsWe have shown that the presence of collagen-I, the main constituent of the ECM, increases the post-translational phosphorylation of Annexin A2 and subsequently causes the translocation of Annexin A2 to the extracellular surface. In the presence of collagen-I, we identified fibronectin as a novel interactor of Annexin A2, using mass spectrometry analysis. We then demonstrated that reducing Annexin A2 expression decreases the degradation of fibronectin by cancer cells and this effect on fibronectin turnover is increased according to collagen-I abundance.DiscussionOur results suggest that Annexin A2's role in promoting cancer progression is mediated by collagen-I and Annexin A2 maybe a therapeutic target in the bi-directional cross-talk between cancer cells and ECM remodeling that supports metastatic cancer progression.

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“…Abnormalities in the distribution of receptors for fibronectin on the surface of tumor cells were also highlighted. In general, fibronectin expression in breast cancer is associated with adverse clinical outcomes [ 268 , 269 , 270 , 271 , 272 , 273 , 274 , 275 ].…”

Section: Breast Cancermentioning

confidence: 99%

The Role of Extracellular Matrix Proteins in Breast Cancer

Lepucki

Orlińska

Mielczarek‐Palacz

et al. 2022

JCM

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The extracellular matrix is a structure composed of many molecules, including fibrillar (types I, II, III, V, XI, XXIV, XXVII) and non-fibrillar collagens (mainly basement membrane collagens: types IV, VIII, X), non-collagenous glycoproteins (elastin, laminin, fibronectin, thrombospondin, tenascin, osteopontin, osteonectin, entactin, periostin) embedded in a gel of negatively charged water-retaining glycosaminoglycans (GAGs) such as non-sulfated hyaluronic acid (HA) and sulfated GAGs which are linked to a core protein to form proteoglycans (PGs). This highly dynamic molecular network provides critical biochemical and biomechanical cues that mediate the cell–cell and cell–matrix interactions, influence cell growth, migration and differentiation and serve as a reservoir of cytokines and growth factors’ action. The breakdown of normal ECM and its replacement with tumor ECM modulate the tumor microenvironment (TME) composition and is an essential part of tumorigenesis and metastasis, acting as key driver for malignant progression. Abnormal ECM also deregulate behavior of stromal cells as well as facilitating tumor-associated angiogenesis and inflammation. Thus, the tumor matrix modulates each of the classically defined hallmarks of cancer promoting the growth, survival and invasion of the cancer. Moreover, various ECM-derived components modulate the immune response affecting T cells, tumor-associated macrophages (TAM), dendritic cells and cancer-associated fibroblasts (CAF). This review article considers the role that extracellular matrix play in breast cancer. Determining the detailed connections between the ECM and cellular processes has helped to identify novel disease markers and therapeutic targets.

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Collagen and fibronectin promote an aggressive cancer phenotype in breast cancer cells but drive autonomous gene expression patterns

Cited by 13 publications

References 35 publications

Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer

Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer

Collagen-I influences the post-translational regulation, binding partners and role of Annexin A2 in breast cancer progression

The Role of Extracellular Matrix Proteins in Breast Cancer

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