Fibronectin (FN) type III domain containing 3B (FNDC3B), a member of the FN family, regulates the invasion and metastasis of cells in numerous tumor types.
Pterostilbene prevents AKT-ERK axis-mediated polymerization of surface fibronectin on suspended lung cancer cells independently of apoptosis and suppresses metastasis.
UMFNP-CREKA is recruited to the margin of tumor metastases by the binding of CREKA with fibrin-fibronectin complexes, which are abundant around tumors, and then release of manganese ions (Mn<sup>2+</sup> ) to the metastasis in response to pathological parameters (mild acidity and elevated H<sub>2</sub> O<sub>2</sub> ).
Bioinformatics analyses suggested that the simultaneous manipulation of multiple targets in proliferation pathways (such as epidermal growth factor receptor, fibroblast growth factor receptor 2, human epidermal growth factor receptor 2, proliferating cell nuclear antigen, and insulin like growth factor 2) and the process of cancer metastasis (collagen families, fibronectin 1 and matrix metalloproteinases families) might largely account for the mechanisms of the 13 herbs against gastric adenocarcinoma.A network pharmacology method was introduced to decipher the underlying mechanisms of CHM, which provides a good foundation for herbal research based on clinical data.
High stromal FN content facilitates tumor cell metastasis by promoting morphological changes and improving the motility and migratory ability of ESCC cells.
A functional blockade of Wnt/β-catenin pathway by either a pharmacological Wnt-antagonist, WntC59, sulidac sulfide, or β-catenin (functional read out of Wnt/β-catenin pathway) SiRNA mediated genetic manipulation demonstrated that a functional perturbation of the pathway is causal to the metastasis- associated phenotypes including fibronectin-directed migration, F-actin organization, and invasion in TNBC cells.
1) It is possible to differentiate between metastatic and non-metastatic PC cells on the basis of CD44v10 expression; 2) CD44v10 seems to be involved in mediating fibronectin adhesion in vitro and in counteracting metastases in vivo.
In this study, we evaluated the ability of ATN-161 (Ac-PHSCN-NH2), a 5-mer capped peptide derived from the synergy region of fibronectin that binds to alpha5beta1 and alphavbeta3 in vitro, to block breast cancer growth and metastasis.
It does so, in part, by upregulating expression and activity of matrix remodeling enzymes that lead to increased cleavage of fibronectin and spreading of tumor cells.
Finally, we discovered that one of the mechanisms explaining SERPINA5 inhibition of HCC metastasis is through direct interaction with fibronectin and disruption of the fibronectin-integrin signaling pathway.
Because adhesion to the extracellular matrix (ECM) is required for invasion and metastasis, we hypothesized that pericellular HA mediates adhesion to ECM proteins such as laminin, collagen, and fibronectin and that inhibition of HA production or removal of HA by digestion with hyaluronidase would impair adhesion.
Since the steady state level of LR mRNA has been shown to control the number of receptors expressed at the cell surface, these results suggest that contact of the cancer cells with laminin and fibronectin in the host matrix may be an important regulatory mechanism by which cancer cells maintain a high number of LR at their cell surface as they progress through the several steps of tumoral invasion and metastasis.
Although numerous studies suggest a role of tumor cell fibronectin interaction in tumor metastasis, differential integrin expression on tumor cells has, however, not been correlated with metastatic capabilities.
Specifically, miR-30c, a FHIT-upregulated microRNA, contributes to FHIT function in suppression of EMT and metastasis by directly targeting metastasis genes Metadherin (MTDH), High-mobility group AT-hook 2 (HMGA2), and the mesenchymal markers, Vimentin (VIM) and Fibronectin (FN1), in human lung cancer.
The results showed that the number of cells attached to FN-matrix increases upon treatment of the cells with staurosporine, indicating that the change of N-glycosylation of the FN-receptor promotes cell adhesion to the extracellular matrix, which may lead to the suppression of metastasis of cancer cells.
Immunoblotting and quantitative real time (RT)-PCR analysis revealed that vanillin down-regulates HIF-1α protein accumulation and the transcripts of HIF-1α target genes related to cancer metastasis including fibronectin 1 (<i>FN1</i>), lysyl oxidase-like 2 (<i>LOXL2</i>), and urokinase plasminogen activator receptor (<i>uPAR</i>).
The present study, therefore, may explain the role of MIA in metastasis in vivo, and supports a model in which the binding of human MIA to type III repeats of fibronectin competes with integrin binding, thus detaching cells from the extracellular matrix.