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: Based on the ability of WNT10B to have clinical significance in TNBC, we hypothesize if HMGA2 would be able to have the same outcome. To this end we conducted IHC analysis for HMGA2 in 14 samples from African-Americans (AA; from The University of Chicago), 31 Caucasian-American samples (from Cedars-Sinai Medical Center) and 14 German samples. There is strong expression of nuclear HMGA2 protein in the TNBC samples (Fig 6A and Supporting Information Fig S6A–C). Furthermore, nuclear HMGA2 expression is restricted to TNBC as it was not detectable in ERα+, PR+, HER2+ and triple positive (TP) breast cancer samples (Fig 6B). More interestingly, HMGA2 expression was not detected at all or at very low levels in four adjacent ‘normal’ breast tissue biopsies, which are from the AA TNBC samples (Supporting Information Fig S6D). We determined the frequency of nuclear HMGA2 expression to be >80% in our TNBC sample set (Supporting Information Fig S6E).
Affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.