ESR1 and cancer: The results showed that the depletion of only BIG3 led to interactions between endogenous PHB2 released from BIG3 with nuclear ERα but that the depletion of BIG3 and KPNA1, KPNA5, and KPNA6 did not (Fig 5A), indicating that PHB2 binding to nuclear ERα in cancer cells is KPNA-mediated.