Open AccessIncreased SIX‐1 expression promotes breast cancer metastasis by regulating lncATB‐miR‐200s‐ZEB1 axis
Author(s) -
Zhu Lizhe,
Jiang Siyuan,
Yu Shibo,
Liu Xiaoxu,
Pu Shengyu,
Xie Peiling,
Chen Heyan,
Liao Xiaoqin,
Wang Ke,
Wang Bin
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.15185
Subject(s) - gene knockdown , cancer research , metastasis , in vivo , homeobox , small hairpin rna , breast cancer , microrna , cxcr4 , cell migration , biology , in vitro , transcription factor , cancer , medicine , cell culture , gene , receptor , genetics , chemokine
Patients with advanced breast cancer (BC) showed a higher incidence of regional and distant metastases. Sine oculis homeobox homolog 1 (SIX‐1) has been confirmed to be a key tumorigenic and metastatic regulator in BC progression. Yet, molecular mechanisms behind SIX‐1‐induced BC metastases remain largely unknown. Here we found that SIX‐1 was frequently up‐regulated in BC and correlated with poor outcomes when tested in human BC tissue microarray. Then, we manipulated the expression of SIX‐1 by via shRNA‐mediated knockdown and lentivirus‐mediated overexpression. Transwell assay in vitro and lung metastases model of nude mice in vivo showed that SIX‐1 promoted BC cell invasion and migration in vitro, and facilitated metastases in vivo . Mechanistically, SIX‐1 could promote the transcription of lncATB, which exerts critical pro‐metastatic role in BC by directly binding to the miR‐200 family, especially for miR‐200c, to induce EMT and promote metastases. In conclusion, SIX‐1 exerts its pro‐metastatic role in BC through lncATB/miR‐200s axis of EMT signalling pathway and could act as an important diagnostic marker as well as a significant therapeutic target for clinically advanced BC.