Research
Integrin activation plays a key role in cancer metastasis. However, a potential cooperative effect between different integrins was unknown in solid tumors. Here, we demonstrate the capacity of CDH6 to promote αIIbβ3 and α2β1 integrin crosstalk, regulating metastatic progression, in ovarian and renal cancer. Based on these findings, our study unveils new strategies for the treatment of ovarian and renal cancer metastasis.
17 Mar 2021
Identified a new therapeutic target against metastatic ovarian cancer
The group led by Dr. Ignacio Casal at the Margarita Salas Center for Biological Research (CSIC) has identified a new therapeutic target for the treatment of ovarian cancer. The work, published in the journal Molecular Oncology, describes the role of cadherin 6 and αIIbβ3 integrin in the invasion and metastatic progression of ovarian cancer.
Ovarian cancer is associated with a high mortality rate. A characteristic feature of advanced ovarian cancer, shared with renal cancer, is the overexpression of cadherin 6 (CDH6). Few studies in the field of metastasis have focused on CDH6 and there are no previous studies of its interaction with integrins in cancer cells. We hypothesized that the RGD-mediated association of CDH6 with different integrins plays a key role in cancer progression and metastasis. Therefore, efforts to understand the role of CDH6 and its interactions in this disease are imperative in order to develop clinical strategies to fight ovarian cancer metastasis.
Bartolome et al. uncover, first, the expression of αIIbβ3 integrin in cancer cells and, second, integrin crosstalk between αIIbβ3 and α2β1, promoted by CDH6, that regulates the metastatic progression in ovarian and renal cancer, providing a clue for better understanding this metastatic progression. In addition, this is the first report of integrin crosstalk in solid tumors. Furthermore, the capacity of cadherin RGD-specific monoclonal antibodies and clinically-approved aIIbb3 inhibitors, i.e. eptifibatide, to inhibit cancer invasion offer a broad therapeutic potential for the treatment of ovarian and renal cancer metastasis.
The relevance of CDH6/αIIbβ3 integrin in multiple cellular processes, including platelet aggregation, platelet-tumor cell interactions, and the metastasis of different tumors, suggests a potential application to other cancer metastases.
Reference: CDH6-activated αIIbβ3 crosstalks with α2β1 to trigger cellular adhesion and invasion in metastatic ovarian and renal cancers. Bartolomé RA, Robles J, Martin-Regalado Á, Pintado-Berninches L, Burdiel M, Jaén M, Aizpurúa C, Imbaud JI, Casal JI. Mol Oncol. 2021 Mar 14. doi: 10.1002/1878-0261.12947. Online ahead of print. PMID: 33715292