Genes & Cancer

Correlation between c-Met and ALDH1 contributes to the survival and tumor-sphere formation of ALDH1 positive breast cancer stem cells and predicts poor clinical outcome in breast cancer

Yuka Nozaki1,5, Shoma Tamori1,5, Masahiro Inada1, Reika Katayama1, Hiromi Nakane1, Osamu Minamishima1, Yuka Onodera1, Makoto Abe1, Shota Shiina1, Kei Tamura1, Daichi Kodama1, Keiko Sato3, Yasushi Hara4, Ryo Abe4, Ryoko Takasawa2, Atsushi Yoshimori6, Nariyoshi Shinomiya7, Sei-ichi Tanuma2 and Kazunori Akimoto1,5

1 Department of Medicinal and Life Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan

2 Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan

3 Department of Information Sciences, Faculty of Science and Technology, Tokyo University of Science, Chiba, Japan

4 Research Institute for Biochemical Sciences, Tokyo University of Science, Chiba, Japan

5 Translational Research Center, Research Institute for Science& Technology, Tokyo University of Science, Chiba, Japan

6 Institute for Theoretical Medicine, Inc., Yokohama, Japan

7 Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Saitama, Japan


Kazunori Akimoto, email:

Keywords: ALDH1, breast cancer, CSC, c-Met

Received: April 03, 2017 Accepted: August 13, 2017 Published: August 22, 2017


c-Met is a receptor-type tyrosine kinase, which is involved in a wide range of cellular responses such as proliferation, motility, migration and invasion. It has been reported to be overexpressed in various cancers. However, the role of c-Met in breast cancer stem cells (CSCs) still remains unclear. We herein, show that c-Met expression is significantly elevated in Basal-like type of breast cancer in comparison with other subtypes. High expression of c-Met strongly correlated with the expression of two CSC markers, ALDH1A3 and CD133 in breast cancers. In addition, breast cancers at tumor stage III-IV expressing both c-Methigh and ALDH1A3high had poor prognosis. Furthermore, treatment with c-Met inhibitors (Crizotinib, Foretinib, PHA-665752 and Tivantinib) in MDA-MB157 cells with high c-Met protein expression resulted in significant suppression in cell viability, contrary to MDA-MB468 cells with low c-Met protein expression. These c-Met inhibitors also suppressed cell viability and tumor-sphere formation of ALDH1high breast cancer cells with high c-Met expression. These results suggest that c-Met in ALDH1 positive CSCs seems to play an important role in breast cancer repopulation. Therefore, we conclude that c-Met is a potential therapeutic target in ALDH1 positive breast CSCs.

PII: 148