Potential Role of E-cadherin in Breast Cancer Metastasis
Posted: Monday, December 2, 2019
Although previous studies indicated that the loss of the cell-adhesion protein E-cadherin was an essential component for breast cancer metastasis, a new study, published as a research letter in Nature, reported that the molecule appears to promote cancer cell survival and allow for metastatic spread. Andrew J. Ewald, PhD, of Johns Hopkins University, Baltimore, and colleagues propose that E-cadherin acts as a survival factor for invasive cancerous pathways during the detachment, dissemination, and seeding phases of metastasis. Identifying methods for the inhibition of E-cadherin may prevent the recurrence of breast cancer.
The investigators tested the genetic requirements for E-cadherin to evaluate its role in breast cancer metastasis. Both mouse and human models of common subtypes of invasive ductal carcinoma (including luminal, basal, and triple-negative breast cancer) were used.
The loss of the E-cadherin gene in all three models seemed to substantially increase cancerous invasion. In a mouse model, tumors with the E-cadherin gene invaded along 6% of their borders, whereas those without the E-cadherin gene invaded along 82% of their borders. However, the loss of E-cadherin did not improve other aspects of metastasis—in fact, most cells that left the primary tumor died, and the few that managed to migrate did not proliferate in new organs and rarely formed new tumors. These results reveal that breast cancer cells seem to require E-cadherin for adhesive connections to survive by limiting reactive oxygen-mediated apoptosis and eventually spread.
“Our future research aims to understand how to target the survival signals related to E-cadherin and prevent metastases from forming, thereby saving patients’ lives,” Dr. Ewald stated in Johns Hopkins Medicine press release.
Disclosure: For full disclosures of the study authors, visit nature.com.
