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.
Original language | English |
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Pages (from-to) | 2739-2751 |
Number of pages | 13 |
Journal | Theranostics |
Volume | 8 |
Issue number | 10 |
DOIs | |
State | Published - 2018 |
Bibliographical note
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.
Publisher Copyright:
© Ivyspring International Publisher.
Keywords
- Basal-like breast cancer (BLBC)
- EMT
- ROR1
- Tumor metastasis
- Twist
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Pharmacology, Toxicology and Pharmaceutics (miscellaneous)