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Guidance of Signaling Activations by Cadherins and Integrins in Epithelial Ovarian Cancer Cells

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ABSTRACT

Epithelial ovarian cancer (EOC) is the deadliest tumor among gynecological cancer in the industrialized countries. The EOC incidence and mortality have remained unchanged over the last 30 years, despite the progress in diagnosis and treatment. In order to develop novel and more effective therapeutic approaches, the molecular mechanisms involved in EOC progression have been thoroughly investigated in the last few decades. At the late stage, peritoneal metastases originate from the attachment of small clusters of cancer cells that shed from the primary site and carried by the ascites adhere to the abdominal peritoneum or omentum. This behavior suggests that cell–cell or cell–matrix adhesion mechanisms regulate EOC growth and dissemination. Complex downstream signalings, which might be influenced by functional cross-talk between adhesion molecules and co-expressed and activated signaling proteins, can affect the proliferation/survival and the migration/invasion of EOC cells. This review aimed to define the impact of the mechanisms of cell–cell, through cadherins, and cell–extracellular matrix adhesion, through integrins, on the signaling cascades induced by membrane receptors and cytoplasmic proteins known to have a role in the proliferation, migration and invasion of EOC cells. Finally, some novel approaches using peptidomimetic ligands to cadherin and integrins are summarized.

No MeSH data available.


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Schematic representation of the the signaling cascades activated in cancer cells by the cross-talk between integrins and RTKs. The arrays indicate: black, signaling cascades; yellow, phosphorylation; discontinuous, possible signaling cascades; blue, trafficking; red, effect. The abbreviations are: RTK, Receptor Tyrosine Kinase; ECM, Extra Cellular Matrix, MAPK, Mitogen Activated Protein Kinase, FAK, Focal Adhesion Kinase; src, Sarcoma viral oncogene; ERK, Extracellular signal-Regulated Kinase.
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ijms-17-01387-f002: Schematic representation of the the signaling cascades activated in cancer cells by the cross-talk between integrins and RTKs. The arrays indicate: black, signaling cascades; yellow, phosphorylation; discontinuous, possible signaling cascades; blue, trafficking; red, effect. The abbreviations are: RTK, Receptor Tyrosine Kinase; ECM, Extra Cellular Matrix, MAPK, Mitogen Activated Protein Kinase, FAK, Focal Adhesion Kinase; src, Sarcoma viral oncogene; ERK, Extracellular signal-Regulated Kinase.

Mentions: Numerous studies suggest that the cooperation between integrins and RTKs exists and exerts a central role in cancer progression regulating invasion, proliferation and survival (see, for review, [89]). Considering that neither α or β subunit possess catalytic activity, it is possible that multiple mechanisms may regulate the cross-talk between integrins and RTKs. Three main types of integrins/RTKs interaction have been identified [90] (Figure 2): (1) integrins can physically bind to RTKs; (2) integrins clustering upon the binding to ECM can enhance signaling pathways that are activated following ligand-dependent RTKs activation; and (3) integrins and RTKs reciprocally control their surface expression.


Guidance of Signaling Activations by Cadherins and Integrins in Epithelial Ovarian Cancer Cells
Schematic representation of the the signaling cascades activated in cancer cells by the cross-talk between integrins and RTKs. The arrays indicate: black, signaling cascades; yellow, phosphorylation; discontinuous, possible signaling cascades; blue, trafficking; red, effect. The abbreviations are: RTK, Receptor Tyrosine Kinase; ECM, Extra Cellular Matrix, MAPK, Mitogen Activated Protein Kinase, FAK, Focal Adhesion Kinase; src, Sarcoma viral oncogene; ERK, Extracellular signal-Regulated Kinase.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037667&req=5

ijms-17-01387-f002: Schematic representation of the the signaling cascades activated in cancer cells by the cross-talk between integrins and RTKs. The arrays indicate: black, signaling cascades; yellow, phosphorylation; discontinuous, possible signaling cascades; blue, trafficking; red, effect. The abbreviations are: RTK, Receptor Tyrosine Kinase; ECM, Extra Cellular Matrix, MAPK, Mitogen Activated Protein Kinase, FAK, Focal Adhesion Kinase; src, Sarcoma viral oncogene; ERK, Extracellular signal-Regulated Kinase.
Mentions: Numerous studies suggest that the cooperation between integrins and RTKs exists and exerts a central role in cancer progression regulating invasion, proliferation and survival (see, for review, [89]). Considering that neither α or β subunit possess catalytic activity, it is possible that multiple mechanisms may regulate the cross-talk between integrins and RTKs. Three main types of integrins/RTKs interaction have been identified [90] (Figure 2): (1) integrins can physically bind to RTKs; (2) integrins clustering upon the binding to ECM can enhance signaling pathways that are activated following ligand-dependent RTKs activation; and (3) integrins and RTKs reciprocally control their surface expression.

View Article: PubMed Central - PubMed

ABSTRACT

Epithelial ovarian cancer (EOC) is the deadliest tumor among gynecological cancer in the industrialized countries. The EOC incidence and mortality have remained unchanged over the last 30 years, despite the progress in diagnosis and treatment. In order to develop novel and more effective therapeutic approaches, the molecular mechanisms involved in EOC progression have been thoroughly investigated in the last few decades. At the late stage, peritoneal metastases originate from the attachment of small clusters of cancer cells that shed from the primary site and carried by the ascites adhere to the abdominal peritoneum or omentum. This behavior suggests that cell–cell or cell–matrix adhesion mechanisms regulate EOC growth and dissemination. Complex downstream signalings, which might be influenced by functional cross-talk between adhesion molecules and co-expressed and activated signaling proteins, can affect the proliferation/survival and the migration/invasion of EOC cells. This review aimed to define the impact of the mechanisms of cell–cell, through cadherins, and cell–extracellular matrix adhesion, through integrins, on the signaling cascades induced by membrane receptors and cytoplasmic proteins known to have a role in the proliferation, migration and invasion of EOC cells. Finally, some novel approaches using peptidomimetic ligands to cadherin and integrins are summarized.

No MeSH data available.


Related in: MedlinePlus