Abstract
Rationale: Twist is a key transcription factor for induction of epithelial-mesenchymal transition (EMT), which promotes cell migration, invasion, and cancer metastasis, confers cancer cells with stem cell-like characteristics, and provides therapeutic resistance. However, the functional roles and targeted genes of Twist in EMT and cancer progression remain elusive.
Methods: The potential targeted genes of Twist were identified from the global transcriptomes of T47D/Twist cells by microarray analysis. EMT phenotype was detected by western blotting and immunofluorescence of marker proteins. The dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the direct transcriptional induction of ROR1 by Twist. A lung metastasis model was used to study the pro-metastatic role of Twist and ROR1 by injecting MDA-MB-231 cells into tail vein of nude mice. Bio-informatics analysis was utilized to measure the metastasis-free survival of breast cancer patients.
Results: Twist protein was proved to directly activate the transcription of ROR1 gene, a receptor of Wnt5a in non-canonical WNT signaling pathway. Silencing of ROR1 inhibited EMT process, cell migration, invasion, and cancer metastasis of basal-like breast cancer (BLBC) cells. Knockdown of ROR1 also ameliorated the pro-metastatic effect of Twist. Furthermore, analyses of clinical specimens indicated that high expression of both ROR1 and Twist tightly correlates with poor metastasis-free survival of breast cancer patients.
Conclusion: ROR1 is a targeted gene of Twist. Twist/ROR1 signaling is critical for invasion and metastasis of BLBC cells.
Document Type
Article
Publication Date
4-9-2018
Digital Object Identifier (DOI)
https://doi.org/10.7150/thno.21477
Funding Information
This work was supported by grants from Science and Technology Program of Guangzhou, China (201508020102) to Tiebang Kang; National Natural Science Foundation of China (81672629), and Science and Technology Program of Guangzhou, China (201707010331) to Jian Shi.
Related Content
Supplementary figures and tables. http://www.thno.org/v08p2739s1.pdf
Repository Citation
Cao, Jingying; Wang, Xin; Dai, Tao; Wu, Yuanzhong; Zhang, Meifang; Cao, Renxian; Zhang, Ruhua; Wang, Gang; Jiang, Rou; Zhou, Binhua P.; Shi, Jian; and Kang, Tiebang, "Twist Promotes Tumor Metastasis in Basal-Like Breast Cancer by Transcriptionally Upregulating ROR1" (2018). Markey Cancer Center Faculty Publications. 106.
https://uknowledge.uky.edu/markey_facpub/106
Supplementary figures and tables.
Notes/Citation Information
Published in Theranostics, v. 8, issue 10, p. 2739-2751.
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