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Skp2 depletion reduces tumor-initiating properties and promotes apoptosis in synovial sarcoma
- Source :
- Translational Oncology, Vol 13, Iss 10, Pp 100809-(2020), Translational oncology, vol 13, iss 10, Translational Oncology
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- Synovial sarcoma (SS) is an aggressive soft-tissue cancer with a poor prognosis and a propensity for local recurrence and distant metastasis. In this study, we investigated whether S phase kinase-associated protein (Skp2) plays an oncogenic role in tumor initiation, progression, and metastasis of SS. Our study revealed that Skp2 is frequently overexpressed in SS specimens and SS18-SSX transgenic mouse tumors, as well as correlated with clinical stages. Next, we identified that genetic depletion of Skp2 reduced mesenchymal and stemness markers, and inhibited the invasive and proliferative capacities of SS cell lines. Furthermore, Skp2 depletion markedly suppressed the growth of SS xenografts tumors. Treatment of SS cell lines with the skp2 inhibitor flavokawain A (FKA) reduced Skp2 expression in a dose-dependent manner and resulted in cell cycle arrest and apoptosis. FKA also suppressed the invasion and tumor-initiating properties in SS, similar to the effects of Skp2 knockdown. In addition, a combination of FKA and conventional chemotherapy showed a synergistic therapeutic efficacy. Taken together, our results suggest that Skp2 plays an essential role in the biology of SS by promoting the mesenchymal state and cancer stemness. Given that chemotherapy resistance is often associated with cancer stemness, strategies of combining Skp2 inhibitors with conventional chemotherapy in SS may be desirable.
- Subjects :
- 0301 basic medicine
Cancer Research
Original article
Clinical Sciences
Oncology and Carcinogenesis
Tumor initiation
Biology
lcsh:RC254-282
Metastasis
03 medical and health sciences
0302 clinical medicine
medicine
SKP2
Oncology & Carcinogenesis
Gene knockdown
Mesenchymal stem cell
Cancer
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Synovial sarcoma
030104 developmental biology
Oncology
Apoptosis
030220 oncology & carcinogenesis
Cancer research
Biochemistry and Cell Biology
Subjects
Details
- Language :
- English
- ISSN :
- 19365233
- Volume :
- 13
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Translational Oncology
- Accession number :
- edsair.doi.dedup.....8b938a90c4f140177528393077664c87