TNPO2 operates downstream of DYNC1I1 and promotes gastric cancer cell proliferation and inhibits apoptosis.

Tytuł:: TNPO2 operates downstream of DYNC1I1 and promotes gastric cancer cell proliferation and inhibits apoptosis.
Autorzy:: Gong L; Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
Wen T; Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
Li Z; Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
Wang Y; Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
Wang J; Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
Che X; Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
Liu Y; Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
Qu X; Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
Źródło:: Cancer medicine [Cancer Med] 2019 Dec; Vol. 8 (17), pp. 7299-7312. Date of Electronic Publication: 2019 Oct 11.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: [Malden, MA] : John Wiley & Sons Ltd., c2012-
MeSH Terms:: Cell Nucleus/*metabolism
Cytoplasmic Dyneins/*metabolism
Stomach Neoplasms/*pathology
beta Karyopherins/*metabolism
Acetylation ; Active Transport, Cell Nucleus ; Apoptosis/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; E1A-Associated p300 Protein ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Histones/metabolism ; Humans ; Promoter Regions, Genetic/genetics ; Sp1 Transcription Factor/metabolism ; Up-Regulation ; beta Karyopherins/genetics
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Grant Information:: 2017ZX09304025 International National Science and Technology Major Project of the Ministry of Science and Technology of China; 81572374 International National Natural Science Foundation of China; 31770963 International National Natural Science Foundation of China; 2016007010 International Science and Technology Plan Project of Liaoning Province; LFWK201706 International The General Projects of Liaoning Province Colleges and Universities; 3110117058 International Discipline Promotion Program of China Medical University; 111-3110118026 International Discipline Promotion Program of China Medical University; 2018225060 International The Key Research and Development Program of Liaoning Province
Contributed Indexing:: Keywords: DYNC1I1; P300; SP1; TNPO2; gastric cancer; proliferation
Substance Nomenclature:: 0 (CDKN1A protein, human)
0 (Cyclin-Dependent Kinase Inhibitor p21)
0 (DYNC1I1 protein, human)
0 (Histones)
0 (Sp1 Transcription Factor)
0 (SP1 protein, human)
0 (TNPO2 protein, human)
0 (beta Karyopherins)
EC 2.3.1.48 (E1A-Associated p300 Protein)
EC 2.3.1.48 (EP300 protein, human)
EC 3.6.4.2 (Cytoplasmic Dyneins)
Entry Date(s):: Date Created: 20191013 Date Completed: 20200924 Latest Revision: 20231213
Update Code:: 20240105
PubMed Central ID:: PMC6885870
DOI:: 10.1002/cam4.2582
PMID:: 31605449
: Czasopismo naukowe

Pełny tekst

The import of proteins into the nucleus plays an important role in tumor development. In addition to the classical nuclear import proteins importin-β and importin-α, there are many nonclassical nuclear import proteins that include TNPO2. The role of TNPO2 as a nonclassical nuclear import protein in tumors is limited. Our previous studies have shown that DYNC1I1 is a poor prognostic factor for gastric cancer and can promote the proliferation and metastasis of gastric cancer cells. An expression profile chip showed that TNPO2 was its potential downstream. DYNC1I1 upregulated TNPO2 expression by upregulating SP1, following which, SP1 recruited and bound to the P300-acetylated TNPO2 promoter region histones, and thus promoted TNPO2 expression. At the same time, TNPO2 promoted gastric cancer cell proliferation and inhibited apoptosis by a mechanism that might be depending on the functional expression of P21.
(© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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