High Expression of c-Met, PKCλ and ALDH1A3 Predicts a Poor Prognosis in Late-stage Breast Cancer
2020
BACKGROUND/AIM: Co-expression of c-Met and ALDH1A3 indicates a poor prognosis in stage III-IV breast cancers and contributes to cell proliferation and tumor formation by ALDH1-positive breast CSCs. PKClambda is overexpressed and contributes to a poor prognosis in several cancers. MATERIALS AND METHODS: A breast cancer genomics data set (METABRIC, n=2509) was downloaded and analyzed, as was the effect c-Met and PKClambda inhibitors on ALDH1(high) cell viability and tumor-sphere formation. RESULTS: c-Met expression correlates with expression of PKClambda in breast cancer. Stage III-IV breast cancer patients with c-Met(high) PKClambda(high) ALDH1A3(high) have a poorer prognosis than patients with c-Met(low) PKClambda(low) ALDH1A3(low) Foretinib and auranofin suppressed cell viability and tumor-sphere formation by ALDH1(high) cells. These results suggest that c-Met and PKClambda are cooperatively involved in cancer progression and contribute to poor prognoses in breast cancer. CONCLUSION: c-Met and PKClambda are potentially useful prognostic markers and therapeutic targets in late-stage breast cancer.
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