The metastasis suppressor NDRG1 down-regulates the epidermal growth factor receptor via a lysosomal mechanism by up-regulating mitogen-inducible gene 6.

ABSTRACT: The metastasis suppressor, N-Myc downstream-regulated gene-1 (NDRG1) inhibits a plethora of oncogenic signaling pathways by down-regulating the epidermal growth factor receptor (EGFR). Herein, we examined the mechanism involved in NDRG1-mediated EGFR down-regulation. NDRG1 overexpression potently increased the levels of mitogen-inducible gene 6 (MIG6), which inhibits EGFR and facilitates its lysosomal processing and degradation. Conversely, silencing NDRG1 in multiple human cancer cell types decreased MIG6 expression, demonstrating the regulatory role of NDRG1. Further, NDRG1 overexpression facilitated MIG6-EGFR association in the cytoplasm, possibly explaining the significantly (p <0.001) increased half-life of MIG6 from 1.6 ± 0.2 h under control conditions to 7.9 ± 0.4 h af

SUBMITTER: Menezes SV 

PROVIDER: S-EPMC6422098 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature