DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathway.
DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathway.
复制标题
DOI：
10.3389/fonc.2022.1036401
复制
发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
骨肉瘤（OS）是一种原发性骨恶性肿瘤，其特点是化疗耐药和高复发率，预后差。DJ-1（PARK 7）是已知的癌基因，其异常表达与多种类型的恶性肿瘤的不良预后有关。本研究发现DJ-1的上调表达与OS患者的预后密切相关，其通过调节CDK 4的活性而不是通过氧化机制或AKT途径促进OS细胞的增殖、迁移和体外化疗耐药。DJ-1和CDK 4的结合促进RB磷酸化，导致E2 F1解离到细胞核中以调节细胞周期相关基因的表达。肿瘤异种移植小鼠模型证明DJ-1敲除抑制体内肿瘤生长。提示DJ-1可能通过调节CDK/RB/E2 F1轴影响OS的发生和发展，为OS患者的治疗提供了新的可能。
Osteosarcoma (OS) is a primary malignant tumor of the bone characterized by poor prognosis due to chemotherapy resistance and high recurrence rates. DJ-1 (PARK7) is known as an oncogene and its abnormal expression is related to the poor prognosis of various types of malignant tumors. It was found in this study that upregulated expression of DJ-1 was closely correlated with the prognosis of OS patients by promoting the proliferation, migration and chemotherapy resistance of OS cells in vitro through regulating the activity of CDK4 but not through the oxidation mechanism or AKT pathway. The combination of DJ-1 and CDK4 promoted RB phosphorylation, leading to the dissociation of E2F1 into the nucleus to regulate the expression of cell cycle-related genes. The tumor xenograft mouse model demonstrated that DJ-1 knockout suppressed tumor growth in vivo. All these findings indicate that DJ-1 can affect the occurrence and progression of OS by regulating the CDK/RB/E2F1axis, suggesting a novel therapeutic opportunity for OS patients.
登录
查看更多内容
影响因子：
5.7
作者：
Kawate T;Iwaya K;Koshikawa K;Moriya T;Yamasaki T;Hasegawa S;Kaise H;Fujita T;Matsuo H;Nakamura T;Ishikawa T;Hiroi S;Iguchi-Ariga SM;Ariga H;Murota K;Fujimori M;Yamamoto J;Matsubara O;Kohno N
通讯作者：
Kohno N
影响因子：
11.5
作者：
Dickson, Mark A.
通讯作者：
Dickson, Mark A.
影响因子：
7.9
作者：
Ma, Zhanjun;Yang, Jingjing;Lu, Li
通讯作者：
Lu, Li
影响因子：
1
作者：
Niculescu, Stefan Adrian;Grecu, Dan Cristian;Simionescu, Cristiana Eugenia;Niculescu, Elena Carmen;Stepan, Mioara Desdemona;Stepan, Alex Emilian
通讯作者：
Stepan, Alex Emilian
DOI：
10.1007/978-981-10-6583-5_4
发表时间：
2017-01-01
期刊：
DJ-1/PARK7 PROTEIN: PARKINSON'S DISEASE, CANCER AND OXIDATIVE STRESS-INDUCED DISEASES
影响因子：
--
作者：
Kawate, Takahiko;Tsuchiya, Benio;Iwaya, Keiichi
通讯作者：
Iwaya, Keiichi