ShcD adaptor protein drives invasion of triple negative breast cancer cells by aberrant activation of EGFR signaling.

ABSTRACT: Triple-negative breast cancer (TNBC) is highly metastatic and presents clinical challenges given the lack of targeted therapies. Here, we report that the ShcD phosphotyrosine adaptor protein is upregulated in TNBC, and its expression correlates with overall reduced patient survival and decreased response to chemotherapy. In human breast cancer cells, we demonstrate that ShcD expression promotes cell invasion and reduces adhesion, and that these effects are abrogated by mutating the ShcD phosphotyrosine binding (PTB) domain. Similarly, in a three-dimensional assembloid model, ShcD-expressing spheroids derived from brain metastatic TNBC cells show enhanced infiltration into cerebral organoids. Using a proteomic screen for ShcD binding partners, we identify multiple components of epidermal gr

SUBMITTER: Lau HR 

PROVIDER: S-EPMC12515706 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature