High Expression of c-Met, PKCλ and ALDH1A3 Predicts a Poor Prognosis in Late- stage Breast Cancer

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. PKC lambda 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 PKC lambda inhibitors on ALDH1(high) cell viability and tumor-sphere formation. Results: c-Met expression correlates with expression of PKC lambda in breast cancer. Stage III-IV breast cancer patients with c-Met(high) PKC lambda(high) ALDH1A3(high) have a poorer prognosis than patients with c-Met(low) PKC lambda(low) ALDH1A3(low). Foretinib and auranofin suppressed cell viability and tumor-sphere formation by ALDH1(high) cells. These results suggest that c-Met and PKC lambda are cooperatively involved in cancer progression and contribute to poor prognoses in breast cancer. Conclusion: c-Met and PKC lambda are potentially useful prognostic markers and therapeutic targets in late-stage breast cancer.