Premium
HOXD13 suppresses prostate cancer metastasis and BMP4 ‐induced epithelial‐mesenchymal transition by inhibiting SMAD1
Author(s) -
Xu Fan,
Shangguan Xun,
Pan Jiahua,
Yue Zhiying,
Shen Kai,
Ji Yiyi,
Zhang Weiwei,
Zhu Yinjie,
Sha Jianjun,
Wang Yanqing,
Fan Liancheng,
Dong Baijun,
Wang Qi,
Xue Wei
Publication year - 2021
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33494
Subject(s) - prostate cancer , epithelial–mesenchymal transition , metastasis , cancer research , prostate , biology , tumor progression , carcinogenesis , homeobox , cancer , transcription factor , medicine , gene , genetics
The HOX genes are a group of highly conserved Homeobox‐containing genes that control the body plan organization during development. However, their contributions to tumorigenesis and tumor progression remain uncertain and controversial. Here we provided evidence of tumor‐suppressive activity of HOXD13 in prostate cancer. HOXD13 depletion contributes to more aggressiveness of prostate cancer cells in vitro and in vivo. These effects were corroborated in a metastatic mice model, where we observed more bone metastatic lesions formed by prostate cancer cells with HOXD13 ablation. Mechanistically, HOXD13 prevents BMP4‐induced epithelial‐mesenchymal transition (EMT) by inhibiting mothers against decapentaplegic homolog 1 (SMAD1) transcription. Both bioinformation and our tissue microarray cohort data show that HOXD13 expression inversely correlated in advanced prostate cancer patient specimens. Our findings establish HOXD13 as a negative regulator of prostate cancer progression and metastasis by preventing BMP4/SMAD1 signaling, and potentially suggest new strategies for targeting metastatic prostate cancer.