The third possible mechanism is that the trans-interaction of necin-4 with nectin-4 or nectin-1 affects the degrees of the cis-interaction of nectin-4 with ErbB2, p95-ErbB2, or ErbB2∆Ex16 through their extracellular regions, because in human breast cancer SUM190-PT cells, nectin-4 not only cis-interacts with integrin β4 but also trans-interacts with nectin-1 or nectin-4 and this trans-interaction further promotes anchorage-independent survival through the c-Src signaling cooperatively with integrin β441. The gene discussed is ERBB2; the disease is breast cancer.