| Autor: |
Lijuan Yin, Qinlong Li, Stefan Mrdenovic, Gina Chia-Yi Chu, Boyang Jason Wu, Hong Bu, Peng Duan, Jayoung Kim, Sungyong You, Michael S. Lewis, Gangning Liang, Ruoxiang Wang, Haiyen E. Zhau, Leland W. K. Chung |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Breast Cancer Research, Vol 24, Iss 1, Pp 1-13 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1465-542X |
| DOI: |
10.1186/s13058-022-01502-6 |
| Popis: |
Abstract Background Keratins (KRTs) are intermediate filament proteins that interact with multiple regulatory proteins to initiate signaling cascades. Keratin 13 (KRT13) plays an important role in breast cancer progression and metastasis. The objective of this study is to elucidate the mechanism by which KRT13 promotes breast cancer growth and metastasis. Methods The function and mechanisms of KRT13 in breast cancer progression and metastasis were assessed by overexpression and knockdown followed by examination of altered behaviors in breast cancer cells and in xenograft tumor formation in mouse mammary fat pad. Human breast cancer specimens were examined by immunohistochemistry and multiplexed quantum dot labeling analysis to correlate KRT13 expression to breast cancer progression and metastasis. Results KRT13-overexpressing MCF7 cells displayed increased proliferation, invasion, migration and in vivo tumor growth and metastasis to bone and lung. Conversely, KRT13 knockdown inhibited the aggressive behaviors of HCC1954 cells. At the molecular level, KRT13 directly interacted with plakoglobin (PG, γ-catenin) to form complexes with desmoplakin (DSP). This complex interfered with PG expression and nuclear translocation and abrogated PG-mediated suppression of c-Myc expression, while the KRT13/PG/c-Myc signaling pathway increased epithelial to mesenchymal transition and stem cell-like phenotype. KRT13 expression in 58 human breast cancer tissues was up-regulated especially at the invasive front and in metastatic specimens (12/18) (p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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