In most kinds of animal cells, the centrosome serves as the main microtubule organizing center （MTOC） that nucleates microtubule arrays throughout the cytoplasm to maintain cell structure, cell division and intracel...In most kinds of animal cells, the centrosome serves as the main microtubule organizing center （MTOC） that nucleates microtubule arrays throughout the cytoplasm to maintain cell structure, cell division and intracellular transport. Whereas in epithelial cells, non-centrosomal MTOCs are established in the apical domain for generating asymmetric microtubule fibers and cilia in epithelial cells for the organ morphogenesis during embryonic development. However, the mechanism by which MTOCs localize to the apical domain in epithelial cells remains largely unknown. Here, we show that Mid liplb has a close interaction with γ-tubulin protein, the central component of MTOC, and modulates lumen opening of the neural tube, gut, intestine, and kidney of zebrafish. Knockdown or dominant negative effect of Mid 1ip 1 b resulted in failure of lumen formation of the organs as aforementioned. Moreover, the non-centrosomal MTOCs were unable to orientate to the apical domain in Midliplb knockdown epithelial cells, and the centrosomal MTOCs were inaccurately placed in the apical domain, resulting in defective formation of asymmetric microtubules and misplacement of cilia in the apical domain. These data uncover a molecule that controls the proper localization of MTOCs in the apical domain in epithelial cells for organ morphogenesis during embryonic development.展开更多
Recent evidences show that nervous system acts as a crucial part of cancer microenvironment.Infiltration of nerve fibers into cancer microenvironment has an important active role in cancer progression.The stimulations...Recent evidences show that nervous system acts as a crucial part of cancer microenvironment.Infiltration of nerve fibers into cancer microenvironment has an important active role in cancer progression.The stimulations of both cancer growth and metastasis by members of nervous system such as neurons and glial cells have been demonstrated.However,how the nervous system is built in cancer is largely unknown.Here we show that a fraction of cancer stem cells(CSCs)derived from patients with gastric carcinoma and colorectal carcinoma are capable of producing neurons that are involved in tumor neurogenesis and tumor growth.Cancer stem cell monoclone derived from a single cancer stem cell was able to generate neurons including sympathetic and parasympathetic neurons to take part in the nervous system in cancer tissues.Knocking down the neural cell generating capability of the human CSCs inhibited the growth of xenograft tumors in mouse model.Our data demonstrate that human CSCs are able to produce one of most important components in the cancer microenvironment that are required for cancer development and progression.展开更多
基金supported by the National Basic Research Program of China (to X.M.,2015CB942800)the Nature Science Foundation of China (to H. X. 31671502)
文摘In most kinds of animal cells, the centrosome serves as the main microtubule organizing center （MTOC） that nucleates microtubule arrays throughout the cytoplasm to maintain cell structure, cell division and intracellular transport. Whereas in epithelial cells, non-centrosomal MTOCs are established in the apical domain for generating asymmetric microtubule fibers and cilia in epithelial cells for the organ morphogenesis during embryonic development. However, the mechanism by which MTOCs localize to the apical domain in epithelial cells remains largely unknown. Here, we show that Mid liplb has a close interaction with γ-tubulin protein, the central component of MTOC, and modulates lumen opening of the neural tube, gut, intestine, and kidney of zebrafish. Knockdown or dominant negative effect of Mid 1ip 1 b resulted in failure of lumen formation of the organs as aforementioned. Moreover, the non-centrosomal MTOCs were unable to orientate to the apical domain in Midliplb knockdown epithelial cells, and the centrosomal MTOCs were inaccurately placed in the apical domain, resulting in defective formation of asymmetric microtubules and misplacement of cilia in the apical domain. These data uncover a molecule that controls the proper localization of MTOCs in the apical domain in epithelial cells for organ morphogenesis during embryonic development.
基金This work was supported by the National Basic Research Program of China(to XM 2015CB942800)the Nature Science Foundation of China(to XM 81361120381to CF 81402446).
文摘Recent evidences show that nervous system acts as a crucial part of cancer microenvironment.Infiltration of nerve fibers into cancer microenvironment has an important active role in cancer progression.The stimulations of both cancer growth and metastasis by members of nervous system such as neurons and glial cells have been demonstrated.However,how the nervous system is built in cancer is largely unknown.Here we show that a fraction of cancer stem cells(CSCs)derived from patients with gastric carcinoma and colorectal carcinoma are capable of producing neurons that are involved in tumor neurogenesis and tumor growth.Cancer stem cell monoclone derived from a single cancer stem cell was able to generate neurons including sympathetic and parasympathetic neurons to take part in the nervous system in cancer tissues.Knocking down the neural cell generating capability of the human CSCs inhibited the growth of xenograft tumors in mouse model.Our data demonstrate that human CSCs are able to produce one of most important components in the cancer microenvironment that are required for cancer development and progression.
