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.
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.
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DOI：
10.18632/genesandcancer.148
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发表时间：
2017-07
期刊：
影响因子：
--
通讯作者：
Akimoto K
中科院分区：
文献类型：
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作者：
Nozaki Y;Tamori S;Inada M;Katayama R;Nakane H;Minamishima O;Onodera Y;Abe M;Shiina S;Tamura K;Kodama D;Sato K;Hara Y;Abe R;Takasawa R;Yoshimori A;Shinomiya N;Tanuma SI;Akimoto K
c-Met是一种受体型酪氨酸激酶，参与广泛的细胞反应，如增殖、运动、迁移和侵袭。据报道，它在各种癌症中过表达。然而，c-Met在乳腺癌干细胞（CSC）中的作用仍不清楚。我们在此表明，与其他亚型相比，c-Met表达在基底样型乳腺癌中显著升高。在乳腺癌中，c-Met的高表达与两种CSC标志物ALDH 1A 3和CD 133的表达密切相关。此外，同时表达c-Methigh和ALDH 1A 3 high的III-IV期乳腺癌预后差。此外，在具有高c-Met蛋白表达的MDA-MB 157细胞中用c-Met抑制剂（克唑替尼、Foretinib、PHA-665752和Tivantinib）处理导致细胞活力显著抑制，与具有低c-Met蛋白表达的MDA-MB 468细胞相反。这些c-Met抑制剂还抑制具有高c-Met表达的ALDH 1high乳腺癌细胞的细胞活力和肿瘤球形成。这些结果表明，ALDH 1阳性CSC中的c-Met似乎在乳腺癌再增殖中起重要作用。因此，我们得出结论，c-Met是ALDH 1阳性乳腺CSC的潜在治疗靶点。
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.