近年来,探究KIFs家族成员在肿瘤发生和发展过程中的功能及作用机制已成为研究热点之一。驱动蛋白超家族包含一类保守的微管依赖性分子运动蛋白,具有腺苷三磷酸酶活性和运动特性。驱动蛋白的主动运动支持多种细胞功能,包括有丝分裂、减...近年来,探究KIFs家族成员在肿瘤发生和发展过程中的功能及作用机制已成为研究热点之一。驱动蛋白超家族包含一类保守的微管依赖性分子运动蛋白,具有腺苷三磷酸酶活性和运动特性。驱动蛋白的主动运动支持多种细胞功能,包括有丝分裂、减数分裂和大分子的转运。有丝分裂是真核细胞分裂的过程,涉及将细胞核、细胞质、细胞器和细胞膜分裂成2个子细胞,这些子细胞成分的部分大致相同。这个过程中的任何错误都可能导致细胞死亡、异常(如基因缺失、染色体易位或重复)和癌症。由于有丝分裂复杂且高度调节,驱动蛋白表达或功能的改变可能导致癌变。此外,由于人类癌症是一种涉及异常细胞生长的基因相关疾病,因此靶向驱动蛋白可能会为控制人类癌症创造一种新的策略。KIF18B属于驱动蛋白家族-8,近年来已经发现部分功能并证明其与多种恶性肿瘤有关。In recent years, investigating the functions and underlying mechanisms of KIFs family members in tumorigenesis and tumor development has emerged as a prominent research area. The kinesin superfamily consists of a group of conserved microtubule-dependent molecular motor proteins, which possess adenosine triphosphatase activity and motility properties. The active motility of kinesins is crucial for supporting diverse cellular functions, such as mitosis, meiosis, and macromolecular transport. Mitosis, the process of eukaryotic cell division, involves the partitioning of the nucleus, cytoplasm, organelles, and cell membrane into two daughter cells with approximately identical components. Any aberration during this process can give rise to cell death, genetic anomalies (e.g., gene deletions, chromosomal translocations, or duplications), and cancer. Given the complexity and highly regulated nature of mitosis, changes in kinesin expression or function may trigger carcinogenesis. Moreover, as human cancer is a gene-related disorder characterized by abnormal cell growth, targeting kinesins could potentially offer a novel strategy for cancer control. KIF18B belongs to the kinesin family-8. In recent years, certain functions of KIF18B have been identified, and it has been demonstrated to be associated with various malignant tumors.展开更多
Objective:Osteosarcoma is a common primary highly malignant bone tumor.Kinesin family member 18B(K1F18B)has been identified as a potential oncogene involved in the development and metastasis of several cancer types.Wh...Objective:Osteosarcoma is a common primary highly malignant bone tumor.Kinesin family member 18B(K1F18B)has been identified as a potential oncogene involved in the development and metastasis of several cancer types.While KIF18B overexpression in osteosarcoma tissue is clearly detected,its specific function in the disease process remains to be established.Methods:K IF18B expression was assessed in osteosarcoma tissues and cells.We additionally evaluated the effects of KIF18B on proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.Results:Our results showed overexpression of KIF18B in osteosarcoma tissues and cells.Knockdown of K IF18B induced G1/S phase arrest and significantly inhibited proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.K IF18B regulated P-catenin expression at the transcriptional level by controlling nuclear aggregation of ATF2 and at the post-transcriptional level by interacting with the adenomatous polyposis coli(APC)tumor suppressor gene in osteosarcoma cells.Conclusions:KIF18B plays a carcinogenic role in osteosarcoma by regulating expression ofβ-catenin transcriptionally via decreasing nuclear aggregation of ATF2 or post-transcriptionally through interactions with APC.Our collective findings support the potential utility of KIF18B as a novel prognostic biomarker for osteosarcoma.展开更多
文摘近年来,探究KIFs家族成员在肿瘤发生和发展过程中的功能及作用机制已成为研究热点之一。驱动蛋白超家族包含一类保守的微管依赖性分子运动蛋白,具有腺苷三磷酸酶活性和运动特性。驱动蛋白的主动运动支持多种细胞功能,包括有丝分裂、减数分裂和大分子的转运。有丝分裂是真核细胞分裂的过程,涉及将细胞核、细胞质、细胞器和细胞膜分裂成2个子细胞,这些子细胞成分的部分大致相同。这个过程中的任何错误都可能导致细胞死亡、异常(如基因缺失、染色体易位或重复)和癌症。由于有丝分裂复杂且高度调节,驱动蛋白表达或功能的改变可能导致癌变。此外,由于人类癌症是一种涉及异常细胞生长的基因相关疾病,因此靶向驱动蛋白可能会为控制人类癌症创造一种新的策略。KIF18B属于驱动蛋白家族-8,近年来已经发现部分功能并证明其与多种恶性肿瘤有关。In recent years, investigating the functions and underlying mechanisms of KIFs family members in tumorigenesis and tumor development has emerged as a prominent research area. The kinesin superfamily consists of a group of conserved microtubule-dependent molecular motor proteins, which possess adenosine triphosphatase activity and motility properties. The active motility of kinesins is crucial for supporting diverse cellular functions, such as mitosis, meiosis, and macromolecular transport. Mitosis, the process of eukaryotic cell division, involves the partitioning of the nucleus, cytoplasm, organelles, and cell membrane into two daughter cells with approximately identical components. Any aberration during this process can give rise to cell death, genetic anomalies (e.g., gene deletions, chromosomal translocations, or duplications), and cancer. Given the complexity and highly regulated nature of mitosis, changes in kinesin expression or function may trigger carcinogenesis. Moreover, as human cancer is a gene-related disorder characterized by abnormal cell growth, targeting kinesins could potentially offer a novel strategy for cancer control. KIF18B belongs to the kinesin family-8. In recent years, certain functions of KIF18B have been identified, and it has been demonstrated to be associated with various malignant tumors.
基金grants from the National Natural Science Foundation of China(Grant No.81802689)China International Medical Foundation(Grant No.Z-2014-06-15331)Conflict of interest。
文摘Objective:Osteosarcoma is a common primary highly malignant bone tumor.Kinesin family member 18B(K1F18B)has been identified as a potential oncogene involved in the development and metastasis of several cancer types.While KIF18B overexpression in osteosarcoma tissue is clearly detected,its specific function in the disease process remains to be established.Methods:K IF18B expression was assessed in osteosarcoma tissues and cells.We additionally evaluated the effects of KIF18B on proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.Results:Our results showed overexpression of KIF18B in osteosarcoma tissues and cells.Knockdown of K IF18B induced G1/S phase arrest and significantly inhibited proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.K IF18B regulated P-catenin expression at the transcriptional level by controlling nuclear aggregation of ATF2 and at the post-transcriptional level by interacting with the adenomatous polyposis coli(APC)tumor suppressor gene in osteosarcoma cells.Conclusions:KIF18B plays a carcinogenic role in osteosarcoma by regulating expression ofβ-catenin transcriptionally via decreasing nuclear aggregation of ATF2 or post-transcriptionally through interactions with APC.Our collective findings support the potential utility of KIF18B as a novel prognostic biomarker for osteosarcoma.
