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

Hitomi Motomura, Yuka Nozaki, Chotaro Onaga, Ayaka Ozaki, Shoma Tamori, Taka Aki Shiina, Shotaro Kanai, Chihiro Ohira, Yasushi Hara, Yohsuke Harada, Ryoko Takasawa, Takehisa Hanawa, Sei Ichi Tanuma, Yasunari Mano, Tsugumichi Sato, Keiko Sato, Kazunori Akimoto

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

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. PKCλ 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 PKCλ inhibitors on ALDH1high cell viability and tumor-sphere formation. Results: c-Met expression correlates with expression of PKCλ in breast cancer. Stage III-IV breast cancer patients with c-Methigh PKCλhigh ALDH1A3high have a poorer prognosis than patients with c-Metlow PKCλlow ALDH1A3low. Foretinib and auranofin suppressed cell viability and tumor-sphere formation by ALDH1high cells. These results suggest that c-Met and PKCλ are cooperatively involved in cancer progression and contribute to poor prognoses in breast cancer. Conclusion: c-Met and PKCλ are potentially useful prognostic markers and therapeutic targets in late-stage breast cancer.

Original languageEnglish
Pages (from-to)35-52
Number of pages18
JournalAnticancer research
Volume40
Issue number1
DOIs
Publication statusPublished - 2020

Keywords

  • ALDH1A3
  • Breast cancer
  • C-Met
  • Cancer stem cell
  • PKCλ

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