RIN1 is a breast tumor suppressor and regulator of EGFR trafficking and signaling.

摘要

Tumors typically arise when a single cell acquires a combination of genetic alterations that allow for unchecked proliferation and other oncogenic traits. These acquired changes typically involved the silencing of tumor suppressor genes and/or activation of oncogenes. A central goal in cancer research is to understand these changes and how they contribute to tumor progression so that we can design more effective treatments for cancer patients.;The multi-functional protein RIN1 is silenced in approximately 25% of breast tumor patient samples and several breast cancer cell lines. The first goal of our study was to determine if this silencing was functionally significant in breast cancer progression. This work shows that RIN1 silencing contributes to breast tumorigenesis in vitro and in vivo. Re-expression of RIN1 in breast cancer cell lines with silenced RIN1 reduced tumor cell migration and invasion in Boyden chamber assays and reduced tumor growth of xenografts in nude mice.;RIN1 has several functional interactions that may mediate tumorigenesis, including interactions with the epidermal growth factor receptor (EGFR). Epithelial cells depend on carefully orchestrated endocytosis and intracellular trafficking of EGFR to avoid oncogenic transformation. As such, disruptions in EGFR regulation are commonly implicated in many cancers. The second goal of tins study was to understand the contribution of RIN1 to the regulation of EGFR endocytosis. We found that RIN1 expression enhances degradation of EGER in HeLa RIN1 in mediating signaling from EGFR, acting as cells and we define a dual role for both an activator and an attenuator.