Details

Autor(en) / Beteiligte

• Liu, Yen-Nien
• Yin, JuanJuan
• Barrett, Ben
• Sheppard-Tillman, Heather
• Li, Dongmei
• Casey, Orla M.
• Fang, Lei
• Hynes, Paul G.
• Ameri, Amir H.
• Kelly, Kathleen

Titel

Loss of Androgen-Regulated MicroRNA 1 Activates SRC and Promotes Prostate Cancer Bone Metastasis

Ist Teil von

• Molecular and cellular biology, 2015-06, Vol.35 (11), p.1940-1951

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• Bone metastasis is the hallmark of progressive and castration-resistant prostate cancers. MicroRNA 1 (miR-1) levels are decreased in clinical samples of primary prostate cancer and further reduced in metastases. SRC has been implicated as a critical factor in bone metastasis, and here we show that SRC is a direct target of miR-1. In prostate cancer patient samples, miR-1 levels are inversely correlated with SRC expression and a SRC-dependent gene signature. Ectopic miR-1 expression inhibited extracellular signal-regulated kinase (ERK) signaling and bone metastasis in a xenograft model. In contrast, SRC overexpression was sufficient to reconstitute bone metastasis and ERK signaling in cells expressing high levels of miR-1. Androgen receptor (AR) activity, defined by an AR output signature, is low in a portion of castration-resistant prostate cancer. We show that AR binds to the miR-1-2 regulatory region and regulates miR-1 transcription. Patients with low miR-1 levels displayed correlated low canonical AR gene signatures. Our data support the existence of an AR-miR-1-SRC regulatory network. We propose that loss of miR-1 is one mechanistic link between low canonical AR output and SRC-promoted metastatic phenotypes.