High expression of ID1 facilitates metastasis in human osteosarcoma by regulating the sensitivity of anoikis via PI3K/AKT depended suppression of the intrinsic apoptotic signaling pathway

American Journal of Translational Research

Ya Cao¹  Yang-Fan Lv²  Zhao-Si Zhang³  Guo-Sheng Zhao⁴  Qiao Zhang⁵  Yang Wang⁶ 

[1] Bone and Trauma Center, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, Peoples Republic of China;Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, Peoples Republic of China;Department of Orthopaedics, Childrens Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, Peoples Republic of China;Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, Peoples Republic of China;Department of Pathology, Xinqiao Hospital, Army Medical University, Chongqing 400037, Peoples Republic of China;Department of Rehabilitation, Xinqiao Hospital, Army Medical University, Chongqing 400016, Peoples Republic of China

关键词: Osteosarcoma;    anoikis;    inhibitor of differentiation or DNA binding 1;    metastasis;    biomarker;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

A lack of understanding of the molecular basis underlying the regulation of metastatic disease and its effective therapy are the primary causes of high mortality in osteosarcoma. Thus, new insights into metastases and novel effective targets for metastatic osteosarcoma are urgently required. Anoikis resistance is considered a hallmark of cancer cells with metastatic ability. However, the molecular mechanism of anoikis is poorly understood in osteosarcoma. We applied immunohistochemistry to investigate the correlation between inhibitor of differentiation or DNA binding 1 (ID1) and clinicopathological features, and investigated the correlation between ID1 and the metastatic behavior of osteosarcoma cells, in vitro and in vivo. The results revealed that ID1 is overexpressed in human osteosarcoma tissues, is positively associated with lung metastases, and is a potential biomarker of poor prognosis. Overexpression of ID1 could increase anoikis insensitivity of osteosarcoma cells to facilitate metastasis through the PI3K/AKT-dependent mitochondrial apoptosis pathway. Knockdown of ID1 partly reversed the high potential of metastasis in anoikis-resistant osteosarcoma cells. Our findings revealed, that ID1 is a candidate molecular target for metastatic potential osteosarcoma by highlighting the role of anoikis resistance. In addition ID1 might be a potential predictor of poor prognosis in patients with osteosarcoma.

【 授权许可】

CC BY-NC