Inhibition of fibronectin accumulation suppresses tumor growth

Ghura, Hiba; Keimer, Marin; Au, Alexandra von; Hackl, N.; Klemis, Verena; Nakchbandi, Inaam A.

doi:10.1016/j.neo.2021.06.012

Cited by 14 publications

(12 citation statements)

References 56 publications

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“…An upregulation of fibronectin levels due to detachment has also been demonstrated for lung and breast cancer cell aggregates, and this upregulation was suggested to be important for the development of anoikis resistance and further metastasis [ 209 ]. In a mouse model, a decrease in fibronectin production by cancer cells was shown to inhibit cancer growth due to inhibition of proliferation by decreasing ERK phosphorylation and diminishing YAP expression [ 210 ].…”

Section: Ecm Remodeling and Modification In Cancermentioning

confidence: 99%

The Functional Role of Extracellular Matrix Proteins in Cancer

Popova

Jücker

2022

Cancers

114

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The extracellular matrix (ECM) is highly dynamic as it is constantly deposited, remodeled and degraded to maintain tissue homeostasis. ECM is a major structural component of the tumor microenvironment, and cancer development and progression require its extensive reorganization. Cancerized ECM is biochemically different in its composition and is stiffer compared to normal ECM. The abnormal ECM affects cancer progression by directly promoting cell proliferation, survival, migration and differentiation. The restructured extracellular matrix and its degradation fragments (matrikines) also modulate the signaling cascades mediated by the interaction with cell-surface receptors, deregulate the stromal cell behavior and lead to emergence of an oncogenic microenvironment. Here, we summarize the current state of understanding how the composition and structure of ECM changes during cancer progression. We also describe the functional role of key proteins, especially tenascin C and fibronectin, and signaling molecules involved in the formation of the tumor microenvironment, as well as the signaling pathways that they activate in cancer cells.

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Section: Ecm Remodeling and Modification In Cancermentioning

confidence: 99%

The Functional Role of Extracellular Matrix Proteins in Cancer

Popova

Jücker

2022

Cancers

114

View full text Add to dashboard Cite

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“…In a previous study, the expression of fibronectin 1 was found to be high in the advanced stages of ovarian cancer 34093898. Inhibiting the expression of fibronectin inhibited the growth of breast cancer cells [ 69 ]. Stable knockout of the B7-H3 gene in MGC-803 and MKN-45 gastric cancer cell lines has been shown; B7-H3 is a type I transmembrane protein that affects the PI3K/AKT signaling pathway by regulating fibronectin to inhibit gastric cancer cell apoptosis [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

MCRS1 Expression Regulates Tumor Activity and Affects Survival Probability of Patients with Gastric Cancer

et al. 2022

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Gastric cancer is the fifth most common cancer worldwide and the third most common cause of cancer-related deaths. Surgery remains the first-choice treatment. Chemotherapy is considered in the middle and advanced stages, but has limited success. Microspherule protein 1 (MCRS1, also known as MSP58) is a protein originally identified in the nucleus and cytoplasm that is involved in the cell cycle. High expression of MCRS1 increases tumor growth, invasiveness, and metastasis. The mechanistic relationships between MCSR1 and proliferation, apoptosis, angiogenesis, and epithelial–mesenchymal transition (EMT) remain to be elucidated. We clarified these relationships using immunostaining of tumor tissues and normal tissues from patients with gastric cancer. High MCRS1 expression in gastric cancer positively correlated with Ki-67, Caspase3, CD31, Fibronectin, pAKT, and pAMPK. The hazard ratio of high MCRS1 expression was 2.44 times that of low MCRS1 expression, negatively impacting patient survival.

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“…Another multifunctional adhesive ECM glycoprotein with key roles in tissue repair is fibronectin, that is overexpressed for example, in cancer. [10][11][12] Finally, tissue injury may also trigger the coagulation cascade, resulting in the formation of fibrin (intravascular or extravascular). Fibrin is an insoluble protein formed by enzymatic polymerization of fibrinogen catalyzed by thrombin.…”

Section: Biology Of Ecm Proteinsmentioning

confidence: 99%

“…Impaired collagen and elastin biosynthesis, ineffective or excessive crosslinking and/or degradation by matrix metalloproteinases (MMPs) drive multiple diseases. Another multifunctional adhesive ECM glycoprotein with key roles in tissue repair is fibronectin, that is overexpressed for example, in cancer [10–12] . Finally, tissue injury may also trigger the coagulation cascade, resulting in the formation of fibrin (intravascular or extravascular).…”

Section: Opportunitiesmentioning

confidence: 99%

Extracellular Matrix Targeted MRI Probes

et al. 2022

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Dysregulated remodeling of the extracellular matrix (ECM) can lead to excessive accumulation of ECM proteins (primarily collagen, elastin/ tropoelastin, fibronectin and fibrin) resulting in tissue fibrosis. In many pathologies, changes in the molecular pattern of ECM components have been related to the progression and severity of fibrosis. Thus, magnetic resonance imaging (MRI) probes sensing specific ECM components hold promise for accurate staging of fibrotic diseases. This paper focuses on gadolinium-based contrast agents (GBCA) targeted to ECM components, including structural proteins and enzymes. According to available examples, they can be grouped into: 1) GBCA conjugated to targeting vectors that recognize and noncovalently bind to specific sites on the molecular target; 2) GBCA carrying a reactive chemical function able to bind covalently to the complementary chemical function of the molecular target; and 3) enzyme-responsive probes, whose relaxivity and pharmacokinetics change after enzymatic processing. Pros and cons of each approach are discussed.

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Inhibition of fibronectin accumulation suppresses tumor growth

Cited by 14 publications

References 56 publications

The Functional Role of Extracellular Matrix Proteins in Cancer

The Functional Role of Extracellular Matrix Proteins in Cancer

MCRS1 Expression Regulates Tumor Activity and Affects Survival Probability of Patients with Gastric Cancer

Extracellular Matrix Targeted MRI Probes

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