WNT10B/β-catenin signalling induces HMGA2 and proliferation in metastatic triple-negative breast cancer.
Bottom Line: Treatment of mouse and human triple-negative tumour cells with two Wnt/β-catenin pathway modulators or siRNA to HMGA2 decreases HMGA2 levels and proliferation.We demonstrate that WNT10B has epistatic activity on HMGA2, which is necessary and sufficient for proliferation of TNBC cells.Furthermore, HMGA2 expression predicts relapse-free-survival and metastasis in TNBC patients.
Affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.Show MeSH
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Mentions: To gain mechanistic insights on how Wnt10b regulates HMGA2 expression we turned to our previously published mouse cell line system NMuMG (NMG) and NMuMG-Wnt10b (NMG-10b; Miranda-Carboni et al, 2008). NMG and NMG-10b cells were synchronized in early G1 by maintenance at 100% confluency for 2–3 days. Cells were then released and harvested at various times for analysis by qt-PCR. NMG-10b cell lines induce five- to eightfold greater Hmga2 expression, at all-time points, than the control parental cell line NMG (Fig 3A). We also silenced Hmga2 in the NMG-10b cell line utilizing a Lentiviral-shHmga2 system to verify that the increased proliferation was due to HMGA2 expression. We observed decreased proliferation (>35%) after Hmga2 silencing, but not restored to NMG parental proliferation levels (Supporting Information Fig S3C).
Affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.