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The interplay between GTP cyclohydrolase and the HSP90 chaperone machinery induces epithelial-to-mesenchymal transition through epidermal growth factor receptor signaling in breast cancer

ABSTRACT: GTP cyclohydrolase (GTPCH) is encoded by the GCH1 gene. Its physiological activity is tightly regulated for neurotransmission, immune and vascular functions. We have shown previously that GTPCH is highly expressed in breast tumors. However, the protumorigenic mechanisms of GTPCH remain unknown. Here we show that GTPCH transforms the immortalized MCF10A breast epithelia and induces epithelial-to-mesenchymal transition (EMT). GTPCH-induced EMT is mediated by epidermal growth factor receptor (EGFR), through HSP90 and activator of HSP90 ATPase1 (AHA1). The GCH1 knockout or inhibition attenuates breast tumor growth in vitro and in vivo, and sensitizes the cells to hormone therapy in cultures. High GCH1 expression is significantly correlated with worse prognosis, chiefly ER+, PR+ and tamoxifen-treated tumors. Thus, GTPCH is an emerged cancer target.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Breast Epithelial Cell, Epithelial Cell

DISEASE(S): Breast Cancer

SUBMITTER: Roman Fischer

LAB HEAD: Roman Fischer

PROVIDER: PXD019676 | Pride | 2022-05-11

REPOSITORIES: Pride

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