Fibronectin in malignancy: Cancer-specific alterations, protumoral effects, and therapeutic implications

Rick, Jonathan W.; Chandra, Ankush; Ore, Cecilia Dalle; Nguyen, Alan; Yagnik, Garima; Aghi, Manish K.

doi:10.1053/j.seminoncol.2019.08.002

Cited by 77 publications

(80 citation statements)

References 74 publications

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“…Overall, our results support the role of the cancer microenvironment in tumor progression and prognosis. Our results also indicate, together with the results obtained by others [9], that fibronectin and periostin play the role of extracellular drivers of malignancy.…”

Section: Discussionsupporting

confidence: 90%

“…It seems that the main mechanism is based on the activation of the focal adhesion kinase (FAK). Downstream FAK/Src signaling can have very diverse cellular effects: from the induction of epithelial to mesenchymal transition (EMT) and acquisition of invasive phenotype, to providing proliferative signaling and even inducing antiapoptotic activity (reviewed in: [6,9]). It was confirmed by Mitra et al that such signaling occurs in ovarian cancer cells: fibronectin binding to α5β1-integrin leads to a direct association of α5-integrin with the c-Met kinase, activating it in a ligand-independent manner.…”

Section: The Role Of Fibronectin In Ovarian Cancermentioning

confidence: 99%

“…Making use of fibronectin in therapy is based on the assumption that, in adults, alternatively-spliced fibronectin variants containing extra domains A and B (EDA/EDB) are primarily limited to sites of malignancy [9,40]. One strategy which has been tested, utilizes recombinant human antibody L19 (specific to the EDB) fused with cytokines such as interleukin 2 (IL2) or tumor necrosis factor α (TNFα).…”

Section: The Role Of Fibronectin In Ovarian Cancermentioning

confidence: 99%

“…Cellular fibronectin has many functions in physiology, related with cell adhesion, growth, migration, and differentiation, playing important role e.g., in embryonic development and wound healing; reviewed in: [6][7][8]. In addition, fibronectin expression has been observed in several cancers; reviewed in: [9,10]. Functional studies demonstrate that fibronectin stimulates ovarian cancer cells proliferation and promotes metastasis by regulating ovarian cancer cells adhesion and invasion [11], reviewed in: [12].…”

Section: Introductionmentioning

confidence: 99%

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Fibronectin and Periostin as Prognostic Markers in Ovarian Cancer

Kujawa

Zembala‐Nożyńska

Cortez

et al. 2020

Cells

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Previously, based on a DNA microarray experiment, we identified a 96-gene prognostic signature associated with the shorter survival of ovarian cancer patients. We hypothesized that some differentially expressed protein-coding genes from this signature could potentially serve as prognostic markers. The present study was aimed to validate two proteins, namely fibronectin (FN1) and periostin (POSTN), in the independent set of ovarian cancer samples. Both proteins are mainly known as extracellular matrix proteins with many important functions in physiology. However, there are also indications that they are implicated in cancer, including ovarian cancer. The expression of these proteins was immunohistochemically analyzed in 108 surgical samples of advanced ovarian cancer (majority: high-grade serous) and additionally on tissue arrays representing different stages of the progression of ovarian and fallopian tube epithelial tumors, from normal epithelia, through benign tumors, to adenocarcinomas of different stages. The correlation with clinical, pathological, and molecular features was evaluated. Kaplan–Meier survival analysis and Cox-proportional hazards models were used to estimate the correlation of the expression levels these proteins with survival. We observed that the higher expression of fibronectin in the tumor stroma was highly associated with shorter overall survival (OS) (Kaplan–Meier analysis, log-rank test p = 0.003). Periostin was also associated with shorter OS (p = 0.04). When we analyzed the combined score, calculated by adding together individual scores for stromal fibronectin and periostin expression, Cox regression demonstrated that this joint FN1&POSTN score was an independent prognostic factor for OS (HR = 2.16; 95% CI: 1.02–4.60; p = 0.044). The expression of fibronectin and periostin was also associated with the source of ovarian tumor sample: metastases showed higher expression of these proteins than primary tumor samples (χ2 test, p = 0.024 and p = 0.032). Elevated expression of fibronectin and periostin was also more common in fallopian cancers than in ovarian cancers. Our results support some previous observations that fibronectin and periostin have a prognostic significance in ovarian cancer. In addition, we propose the joint FN1&POSTN score as an independent prognostic factor for OS. Based on our results, it may also be speculated that these proteins are related to tumor progression and/or may indicate fallopian–epithelial origin of the tumor.

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Section: Discussionsupporting

confidence: 90%

Section: The Role Of Fibronectin In Ovarian Cancermentioning

confidence: 99%

Section: The Role Of Fibronectin In Ovarian Cancermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Fibronectin and Periostin as Prognostic Markers in Ovarian Cancer

Kujawa

Zembala‐Nożyńska

Cortez

et al. 2020

Cells

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“…We also observed stimulation by laminin, consistent with known biology 365 and the observation that invadopodia form at contact sites with basement membrane 366(Schoumacher et al, 2010). We also saw more invadopodia on fibronectin, an abundant ECM 367 protein with appreciated roles in cancer(Rick et al, 2019). But the most prominent ECM inducer 368 of invadopodia was tropoelastin, the soluble precursor of the cross-linked ECM protein elastin 369(Vindin et al, 2019).…”

supporting

confidence: 82%

Crosstalk between invadopodia and the extracellular matrix

Iizuka

Leon

Gribbin

et al. 2020

Preprint

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1The scaffold protein Tks5α is required for invadopodia-mediated cancer invasion both in vitro and 2 in vivo. We have previously also revealed a role for Tks5 in tumor cell growth using three-3 dimensional (3D) culture model systems and mouse transplantation experiments. Here we use 4 both 3D and high-density fibrillar collagen (HDFC) culture to demonstrate that native type I 5 collagen, but not a form lacking the telopeptides, stimulated Tks5-dependent growth, which was 6 dependent on the DDR collagen receptors. We used microenvironmental microarray (MEMA) 7 technology to determine that laminin, collagen I, fibronectin and tropoelastin also stimulated 8 invadopodia formation. A Tks5α-specific monoclonal antibody revealed its expression both on 9 microtubules and at invadopodia. High-and super-resolution microscopy of cells in and on 10 collagen was then used to place Tks5α at the base of invadopodia, separated from much of the 11 actin and cortactin, but coincident with both matrix metalloprotease and cathepsin proteolytic 12 activity. Inhibition of the Src family kinases, cathepsins or metalloproteases all reduced 13 invadopodia length but each had distinct effects on Tks5α localization. These studies highlight 14 the crosstalk between invadopodia and extracellular matrix components, and reveal the 15 invadopodium to be a spatially complex structure. 16 17

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Fibronectin enhances tumor metastasis through B7‐H3 in clear cell renal cell carcinoma

et al. 2021

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B7-H3 plays an important role in tumor biology, but the molecular mechanism underlying the role of B7-H3 in tumor metastasis remains unclear. Here, our analysis of the TCGA database suggested that B7-H3 expression is associated with poor prognosis of patients with clear cell renal cell carcinoma (ccRCC). B7-H3 knockdown affected the expression of metastasis-related genes and significantly suppressed the metastasis of ccRCC cells, but had no significant effect on the proliferation of ccRCC cells. Database analysis revealed a strong positive correlation between B7-H3 and Fibronectin (FN) in ccRCC cells, and further study also confirmed that FN interacts with B7-H3. Silencing FN expression inhibited the migration and invasion of ccRCC cells, whereas exogenous FN promoted the

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Fibronectin in malignancy: Cancer-specific alterations, protumoral effects, and therapeutic implications

Cited by 77 publications

References 74 publications

Fibronectin and Periostin as Prognostic Markers in Ovarian Cancer

Fibronectin and Periostin as Prognostic Markers in Ovarian Cancer

Crosstalk between invadopodia and the extracellular matrix

Fibronectin enhances tumor metastasis through B7‐H3 in clear cell renal cell carcinoma

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