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Hematopoietic cell kinase enhances osteosarcoma development via the MEK/ERK pathway |
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| Authors: | Weibo Liu Teng Li Wenhao Hu Quanbo Ji Fanqi Hu Qi Wang Xiaoqing Yang Dengbin Qi Hui Chen Xuesong Zhang |
| Affiliation: | 1. Department of Orthopaedics, The Fourth Medical Centre, Chinese PLA General Hospital, Beijing, China Contribution: Conceptualization (lead), Formal analysis (equal), Investigation (equal), Methodology (equal), Writing - original draft (equal), Writing - review & editing (equal);2. Department of Orthopaedics, The Fourth Medical Centre, Chinese PLA General Hospital, Beijing, China Contribution: Conceptualization (equal), Formal analysis (equal), Investigation (equal), Methodology (lead), Writing - original draft (equal), Writing - review & editing (equal);3. Department of Orthopaedics, The Fourth Medical Centre, Chinese PLA General Hospital, Beijing, China Contribution: Conceptualization (equal), Formal analysis (lead), Investigation (equal), Methodology (equal), Resources (equal), Software (equal), Writing - original draft (equal), Writing - review & editing (equal);4. Department of Orthopaedics, The Fourth Medical Centre, Chinese PLA General Hospital, Beijing, China Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal);5. Department of Orthopaedics, The Fourth Medical Centre, Chinese PLA General Hospital, Beijing, China Contribution: Software (equal), Writing - original draft (equal), Writing - review & editing (equal);6. Department of Orthopaedics, The Fourth Medical Centre, Chinese PLA General Hospital, Beijing, China Contribution: Methodology (equal), Writing - original draft (equal), Writing - review & editing (equal);7. Department of Orthopaedics, The Fourth Medical Centre, Chinese PLA General Hospital, Beijing, China Contribution: Conceptualization (equal), Investigation (equal), Methodology (equal), Writing - original draft (equal), Writing - review & editing (equal);8. Department of Orthopaedics, The Fourth Medical Centre, Chinese PLA General Hospital, Beijing, China Contribution: Investigation (equal), Methodology (equal), Writing - original draft (equal), Writing - review & editing (equal);9. College of Life Sciences, East China Normal University, Shanghai, China;10. Department of Orthopaedics, The Fourth Medical Centre, Chinese PLA General Hospital, Beijing, China |
| Abstract: | Osteosarcoma (OS) is a sarcoma with high rates of pulmonary metastases and mortality. The mechanisms underlying tumour generation and development in OS are not well-understood. Haematopoietic cell kinase (HCK), a vital member of the Src family of kinase proteins, plays crucial roles in cancer progression and may act as an anticancer target; however, the mechanism by which HCK enhances OS development remains unexplored. Therefore, we investigated the role of HCK in OS development in vitro and in vivo. Downregulation of HCK attenuated OS cell proliferation, migration and invasion and increased OS cell apoptosis, whereas overexpression of HCK enhanced these processes. Mechanistically, HCK expression enhanced OS tumorigenesis via the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; HCK upregulation increased the phosphorylation of MEK and ERK and promoted epithelial-mesenchymal transition, with a reduction in E-cadherin in vitro. Furthermore, HCK downregulation decreased the tumour volume and weight in mice transplanted with OS cells. In conclusion, HCK plays a crucial role in OS tumorigenesis, progression and metastasis via the MEK/ERK pathway, suggesting that HCK is a potential target for developing treatments for OS. |
| Keywords: | cell migration ERK signalling pathway HCK MEK osteosarcoma tumorigenesis |