Open AccessSanguinarine disrupts the colocalization and interaction of HIF‐1α with tyrosine and serine phosphorylated‐STAT3 in breast cancer
Author(s) -
Su Qi,
Wang Jingjing,
Fan Mengying,
Ghauri Mohsin Ahmad,
Ullah Asmat,
Wang Bo,
Dai Bingling,
Zhan Yingzhuan,
Zhang Dongdong,
Zhang Yanmin
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15056
Subject(s) - colocalization , stat3 , sanguinarine , cancer research , stat protein , breast cancer , gene knockdown , in vivo , biology , phosphorylation , cancer , medicine , chemistry , microbiology and biotechnology , apoptosis , alkaloid , biochemistry , botany
Breast cancer is one leading cause of death in females, especially triple‐negative breast cancer (TNBC). Hypoxia is a key feature leading to tumour progression driven by hypoxia‐inducible factor (HIF)‐1α. The aim is to investigate the mechanism of HIF‐1α and signal transducer and activator of transcription‐3 (STAT3) interaction and discover a compound to disrupt the interaction in breast cancer cells. The regulation pattern of HIF‐1α and STAT3 was analysed in hypoxic TNBC cells and patient samples. The effects of a natural alkaloid, sanguinarine, on HIF‐1α and STAT3 colocalization and interaction were evaluated in vitro and mouse xenograft models. We observed strong colocalization of HIF‐1α, p‐STAT3‐Tyr and p‐STAT3‐Ser in TNBC patient samples. Sanguinarine could inhibit the nuclear colocalization and interaction of HIF‐1α with p‐STAT3‐Tyr and p‐STAT3‐Ser in vivo and in vitro. Our results may bring insights to the HIF‐1α/STAT3 interaction in breast cancers and suggest sanguinarine as a promising candidate for HIF‐α/STAT3 inhibition.