Crosstalk between Hh and Wnt signaling promotes osteosarcoma progression

被引:2
作者
Xu, Yao [1 ]
Yu, Peimin [2 ]
Wang, Shilong [1 ]
Jiang, Li [1 ]
Chen, Feiyan [1 ]
Chen, Wenjun [1 ]
机构
[1] Fudan Univ, Huashan Hosp, Dept Orthoped, Shanghai, Peoples R China
[2] Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai, Peoples R China
来源
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY | 2019年 / 12卷 / 03期
基金
中国国家自然科学基金;
关键词
Wnt; Hedgehog; osteosarcoma; beta-catenin; GLI-2; CANCER; PATHWAY; CATENIN; NOTCH;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objective: Osteosarcoma (OS) is the most common primary malignant tumor of bone. Patients with localized osteosarcoma are routinely treated with chemotherapy and surgery. However, many patients eventually relapse after these treatments. Therefore, it is important and urgent to identify better therapeutic strategies. Hedgehog-GLI is responsible for the development of bone and tumorigenesis. Aberrant activation of GLI-2 is correlated with various malignancies including OS. Methods: RT-QPCR and western blot were performed to detect the expression of GLI-2 among human osteosarcoma cell lines U2OS, SaOS and human osteoblast cells HOB-c. siRNA or overexpression method were used to knock down/overexpress GLI-2 or beta-catenin and MTS formazan generation method were applied to study the function of GLI-2 and beta-catenin in the proliferation of OS cells. Results: We showed that GLI-2 is highly expressed in osteosarcoma cell lines. Knockdown of GLI-2 by siRNA decreases osteosarcoma cell proliferation. Further, we showed that knockdown of GLI-2 can decrease the protein level of beta-catenin, and beta-catenin depletion by siRNA could decrease the proliferation of OS cells. Interestingly, overexpression of beta-catenin in GLI-2 knockdown cells partially increased proliferation. Conclusion: These findings suggest Hh/GLI-2-Wnt/beta-catenin crosstalk is required for osteosarcoma cell proliferation. GLI-2 may play a role in the regulation of the expression of beta-catenin in OS cells and beta-catenin may function as downstream effector of crosstalk between Hh and Wnt signaling. GLI-2 may be exploited as a therapeutic target for the treatment of osteosarcoma patients.
引用
收藏
页码:768 / 773
页数:6
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