KRT13 promotes stemness and drives metastasis in breast cancer through a plakoglobin/c-Myc signaling pathway
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13058-022-01502-6 |
| _version_ | 1818333151723782144 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Lijuan Yin |
| collection | DOAJ |
| description | 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 < 0.05). KRT13 up-regulation in primary breast cancer was associated with decreased overall patient survival. Conclusions This study reveals that KRT13 promotes breast cancer cell growth and metastasis via a plakoglobin/c-Myc pathway. Our findings reveal a potential novel pathway for therapeutic targeting of breast cancer progression and metastasis. |
| first_indexed | 2024-12-13T13:47:05Z |
| format | Article |
| id | doaj.art-81fdffabdd8947c88d1526d072f838ac |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-12-13T13:47:05Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-81fdffabdd8947c88d1526d072f838ac2022-12-21T23:43:21ZengBMCBreast Cancer Research1465-542X2022-01-0124111310.1186/s13058-022-01502-6KRT13 promotes stemness and drives metastasis in breast cancer through a plakoglobin/c-Myc signaling pathwayLijuan Yin0Qinlong Li1Stefan Mrdenovic2Gina Chia-Yi Chu3Boyang Jason Wu4Hong Bu5Peng Duan6Jayoung Kim7Sungyong You8Michael S. Lewis9Gangning Liang10Ruoxiang Wang11Haiyen E. Zhau12Leland W. K. Chung13Department of Pathology, West China Hospital, Sichuan UniversityUro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, Department of Medicine, Cedars-Sinai Medical CenterUro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, Department of Medicine, Cedars-Sinai Medical CenterUro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, Department of Medicine, Cedars-Sinai Medical CenterUro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, Department of Medicine, Cedars-Sinai Medical CenterDepartment of Pathology, West China Hospital, Sichuan UniversityUro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, Department of Medicine, Cedars-Sinai Medical CenterDivision of Cancer Biology and Therapeutics, Departments of Surgery and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical CenterDivision of Cancer Biology and Therapeutics, Departments of Surgery and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical CenterDepartment of Pathology, VA Greater Los Angeles Healthcare SystemDepartment of Urology, University of Southern California Keck School of MedicineUro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, Department of Medicine, Cedars-Sinai Medical CenterUro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, Department of Medicine, Cedars-Sinai Medical CenterUro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, Department of Medicine, Cedars-Sinai Medical CenterAbstract 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 < 0.05). KRT13 up-regulation in primary breast cancer was associated with decreased overall patient survival. Conclusions This study reveals that KRT13 promotes breast cancer cell growth and metastasis via a plakoglobin/c-Myc pathway. Our findings reveal a potential novel pathway for therapeutic targeting of breast cancer progression and metastasis.https://doi.org/10.1186/s13058-022-01502-6Breast cancerMetastasisKRT13Plakoglobinγ-Cateninc-Myc |
| spellingShingle | 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 KRT13 promotes stemness and drives metastasis in breast cancer through a plakoglobin/c-Myc signaling pathway Breast Cancer Research Breast cancer Metastasis KRT13 Plakoglobin γ-Catenin c-Myc |
| title | KRT13 promotes stemness and drives metastasis in breast cancer through a plakoglobin/c-Myc signaling pathway |
| title_full | KRT13 promotes stemness and drives metastasis in breast cancer through a plakoglobin/c-Myc signaling pathway |
| title_fullStr | KRT13 promotes stemness and drives metastasis in breast cancer through a plakoglobin/c-Myc signaling pathway |
| title_full_unstemmed | KRT13 promotes stemness and drives metastasis in breast cancer through a plakoglobin/c-Myc signaling pathway |
| title_short | KRT13 promotes stemness and drives metastasis in breast cancer through a plakoglobin/c-Myc signaling pathway |
| title_sort | krt13 promotes stemness and drives metastasis in breast cancer through a plakoglobin c myc signaling pathway |
| topic | Breast cancer Metastasis KRT13 Plakoglobin γ-Catenin c-Myc |
| url | https://doi.org/10.1186/s13058-022-01502-6 |
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