Targeting DYRK1B suppresses the proliferation and migration of liposarcoma cells
- Oncotarget. 2017 Nov 28;9(17):13154-13166. doi: 10.18632/oncotarget.22743.
- 1. Department of Emergency Surgery, ShenZhen People's Hospital, 2nd Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, China, 518020.
- 2. Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
- 3. Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-6902, USA.
Liposarcoma is a common subtype of soft tissue sarcoma and accounts for 20% of all sarcomas. Conventional chemotherapeutic agents have limited efficacy in liposarcoma patients. Expression and activation of serine/threonine-protein kinase dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1B (DYRK1B) is associated with growth and survival of many types of Cancer cells. However, the role of DYRK1B in liposarcoma remains unknown. In this study, we investigated the functional and therapeutic relevance of DYRK1B in liposarcoma. Tissue microarray and immunohistochemistry analysis showed that higher expression levels of DYRK1B correlated with a worse prognosis. RNA interference-mediated knockdown of DYRK1B or targeting DYRK1B with the kinase inhibitor AZ191 inhibited liposarcoma cell growth, decreased cell motility, and induced Apoptosis. Moreover, combined AZ191 with doxorubicin demonstrated an increased anti-cancer effect on liposarcoma cells. These findings suggest that DYRK1B is critical for the growth of liposarcoma cells. Targeting DYRK1B provides a new rationale for treatment of liposarcoma.