Under normal conditions, cells are in homeostasis. Upon the loss of integrin mediated cell-matrix contact, the structure of the focal adhesion complex, including 4.1N, is destroyed, exposing the FERM domain of 4.1N and accelerating the degradation of 14-3-3 through binding with the FERM domain. Functionally, this decrease in 14-3-3 accumulation promotes anoikis and reduces EMT. On the other hand, the loss of 4.1N activates ROCK signaling and leads entosis induced cell-death resistance. EMT enables cancer cells to acquire a migratory and invasive phenotype and allows them to leave the primary tumor; cell death resistance enables the survival of adherent cells in suspension; cancer cells adhere and proliferate in the new environment; the secondary tumor site can be formed.