title: The subcellular distribution and function of MTA1 in cancer differentiation.
abstract: The functions and mechanisms of metastasis-associated protein 1 (MTA1) in cancer progression are still unclear due to a lagged recognition of the subcellular localization. In the present study, using multiple molecular technologies we confirmed for the first time that MTA1 localizes to the nucleus, cytoplasm and nuclear envelope. MTA1 is primarily localized in the nucleus of normal adult tissues but in the cytoplasm of embryonic tissues. While in colon cancer, both distributions have been described. Further investigation revealed that MTA1 localizes on the nuclear envelope in a translocated promoter region (TPR)-dependent manner, while in the cytoplasm, MTA1 shows an obvious localization on microtubules. Both nuclear and cytoplasmic MTA1 are associated with cancer progression. However, these functions may be associated with different mechanisms because only nuclear MTA1 has been associated with cancer differentiation. Overexpression of MTA1 in HCT116 cells inhibited differentiation and promoted proliferation, whereas MTA1 knockdown resulted in cell differentiation and death. Theses results not only suggest that nuclear MTA1 is a good marker for cancer differentiation diagnosis and a potential target for the treatment of cancers but also reveal the necessity to differentially examine the functions of nuclear and cytoplasmic MTA1.
authors: State Key Laboratory of Molecular Oncology; Cancer Institute/Hospital, Peking Union Medical College & ChineseAcademy of Medical Sciences, Beijing, China. Medical Research Center, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China. These authors contribute equally to this work.
authors: Jian
authors: J
authors: Liu
authors: Department of Abdominal Surgery, Cancer Institute/Hospital, Peking Union Medical College & ChineseAcademy of Medical Sciences, Beijing, China. These authors contribute equally to this work.
authors: Dongkui
authors: D
authors: Xu
authors: State Key Laboratory of Molecular Oncology; Cancer Institute/Hospital, Peking Union Medical College & ChineseAcademy of Medical Sciences, Beijing, China. These authors contribute equally to this work.
authors: Haijuan
authors: H
authors: Wang
authors: Department of Gynecology Minimally Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.
authors: Ying
authors: Y
authors: Zhang
authors: Department of Gynecology Minimally Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.
authors: Yanan
authors: Y
authors: Chang
authors: State Key Laboratory of Molecular Oncology; Cancer Institute/Hospital, Peking Union Medical College & ChineseAcademy of Medical Sciences, Beijing, China.
authors: Jinlong
authors: J
authors: Zhang
authors: State Key Laboratory of Molecular Oncology; Cancer Institute/Hospital, Peking Union Medical College & ChineseAcademy of Medical Sciences, Beijing, China.
authors: Jia
authors: J
authors: Wang
authors: State Key Laboratory of Molecular Oncology; Cancer Institute/Hospital, Peking Union Medical College & ChineseAcademy of Medical Sciences, Beijing, China.
authors: Chunxiao
authors: C
authors: Li
authors: State Key Laboratory of Molecular Oncology; Cancer Institute/Hospital, Peking Union Medical College & ChineseAcademy of Medical Sciences, Beijing, China.
authors: Huan
authors: H
authors: Liu
authors: State Key Laboratory of Molecular Oncology; Cancer Institute/Hospital, Peking Union Medical College & ChineseAcademy of Medical Sciences, Beijing, China.
authors: Mei
authors: M
authors: Zhao
authors: State Key Laboratory of Molecular Oncology; Cancer Institute/Hospital, Peking Union Medical College & ChineseAcademy of Medical Sciences, Beijing, China.
authors: Chen
authors: C
authors: Lin
authors: State Key Laboratory of Molecular Oncology; Cancer Institute/Hospital, Peking Union Medical College & ChineseAcademy of Medical Sciences, Beijing, China.
authors: Qimin
authors: Q
authors: Zhan
authors: State Key Laboratory of Molecular Oncology; Cancer Institute/Hospital, Peking Union Medical College & ChineseAcademy of Medical Sciences, Beijing, China.
authors: Changzhi
authors: C
authors: Huang
authors: State Key Laboratory of Molecular Oncology; Cancer Institute/Hospital, Peking Union Medical College & ChineseAcademy of Medical Sciences, Beijing, China.
authors: Haili
authors: H
authors: Qian
mesh_terms: D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism* / Q000648:ultrastructure; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D020869:Gene Expression Profiling; D045325:HCT116 Cells; D057809:HEK293 Cells; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D008870:Microtubules / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators
chemical_list: D014408:Biomarkers, Tumor; C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases