HOXD13 suppresses prostate cancer metastasis and BMP4‐induced epithelial‐mesenchymal transition by inhibiting SMAD1. Issue 12 (6th March 2021)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: International journal of cancer. Volume 148:Issue 12(2021)
• Page Start: 3060
• Page End: 3070
• Publication Date: 2021-03-06
• Subjects: EMT -- HOXD13 -- metastasis -- prostate cancer -- SMAD1; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.33494
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract: 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. Abstract : What's new? While homeobox (HOX) genes are known for regulating organ development and maintaining normal tissues, alterations in their expression potentially influence cancer progression. Here, the authors show that downregulation of HOXD13 in particular is strongly associated with disease progression in prostate cancer patients. Prostate cancer cells harboring low HOXD13 levels exhibited aggressive phenotypes, both in vivo and in vitro . Mechanistically, HOXD13 was found to diminish BMP4‐induced epithelial‐mesenchymal transition by inhibiting SMAD1 transcription, suggesting that HOXD13 negatively regulates prostate cancer progression and metastasis. BMP4‐SMAD1 inhibitors may provide an alternative option for patients whose prostate tumors exhibit HOXD13 downregulation.