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HET0016 attenuates the stemness of breast cancer cells through targeting CYP4Z1
Author(s) -
Liu Hai,
Qin Hai,
Zhou Yi,
Yuan Yin,
Liu Yichen,
Chen Ying,
Yang Yue,
Ni Haiwei,
Xi Tao,
Zheng Lufeng
Publication year - 2021
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.23302
Subject(s) - cd44 , cancer research , cancer stem cell , biology , breast cancer , cd24 , metastasis , cancer , cancer cell , stem cell , transcriptome , cell , microbiology and biotechnology , gene expression , gene , biochemistry , genetics
Ours and other previous studies have shown that CYP4Z1 is specifically and highly expressed in breast cancer, and acts as a promoter for the stemness of breast cancer cells. Here, we explored whether targeting CYP4Z1 could attenuate the stemness of breast cancer cells using HET0016, which has been confirmed to be an inhibitor of CYP4Z1 by us and others. Using the transcriptome‐sequencing analysis, we found that HET0016 suppressed the expression of cancer stem cell (CSC) markers and stem cell functions. Additionally, HET0016 indeed reduced the stemness of breast cancer cells, as evident by the decrease of stemness marker expression, CD44 + /CD24 − subpopulation with stemness, mammary‐spheroid formation, and tumor‐initiating ability. Moreover, HET0016 suppressed the metastatic capability through in vitro and in vivo experiments. Furthermore, we confirmed that HET0016 suppressed CYP4Z1 activity, and HET0016‐induced inhibition on the stemness and metastasis of breast cancer cells was rescued by CYP4Z1 overexpression. Thus, our results demonstrate that HET0016 can attenuate the stemness of breast cancer cells through targeting CYP4Z1.