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Title: CD147-induced cell proliferation is associated with Smad4 signal inhibition

Abstract

CD147 is a multifunctional trans-membrane glycoprotein, which is highly expressed in many cancers. However, the mechanism by which CD147 modulates cell proliferation is not fully understood. The aim of this study is to investigate the role of CD147 in cell proliferation associated with the TGF-β/Smad4 signaling pathway. Here, we used cell viability and clone formation assays in LNCaP prostate cancer cells to demonstrate that CD147 promotes cell proliferation. The luciferase assay and western blotting show that silencing CD147 using shRNA enhances transcription and expression of p21{sup WAF1}. Using immunofluorescence and nuclear-cytoplasmic separation, we show that this is primarily attributed to transport of Smad4 from the cytoplasm to nucleus. Other assays (GST pull-down, co-immunoprecipitation and immunofluorescence) demonstrate that Smad4 is a new interaction partner of CD147, with the Smad4 MH2 domain and CD147 intracellular domain (CD147-ICD) being involved in the interaction. Furthermore, we report that a phosphoserine (pSer) in CD147 (pSer252) is responsible for this interaction and inhibition of the Smad4/p21{sup WAF1} signal that promotes cell proliferation. Our results provide a novel molecular mechanism for CD147-induced cell proliferation associated with Smad4 signal inhibition. - Highlights: • Smad4 interacts with CD147 via the MH2 domain. • CD147 prevents Smad4 translocation into themore » nuclear to regulate p21 transcription. • CD147 inhibits p21 transcription and expression independent on p53. • pCD147-S252 is responsible for interaction with Smad4 and p21 down-regulation.« less

Authors:
 [1];  [1];  [2];  [3]; ; ; ;  [1];  [1];  [4];  [5];  [6];  [5];  [1]
  1. The Key Laboratory of Molecular Epigenetic, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China)
  2. (Japan)
  3. (GCUF), 38000 (Pakistan)
  4. (China)
  5. Dental Hospital, Jilin Universities, Changchun 130021 (China)
  6. Bio-Active Compounds Discovery Research Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198 (Japan)
Publication Date:
OSTI Identifier:
22738158
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 358; Journal Issue: 2; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; GROWTH FACTORS; INHIBITION; INTERACTIONS; MONOCLINIC LATTICES; SIGNALS; TRANSCRIPTION

Citation Formats

Qin, Hui, Rasul, Azhar, Bio-Active Compounds Discovery Research Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Department of Zoology, Faculty of Science and Technology, Government College University Faisalabad, Li, Xin, Masood, Muqaddas, Yang, Guang, Wang, Na, Wei, Wei, Dental Hospital, Jilin Universities, Changchun 130021, He, Xi, Watanabe, Nobumoto, Li, Jiang, and Li, Xiaomeng. CD147-induced cell proliferation is associated with Smad4 signal inhibition. United States: N. p., 2017. Web. doi:10.1016/J.YEXCR.2017.07.003.
Qin, Hui, Rasul, Azhar, Bio-Active Compounds Discovery Research Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Department of Zoology, Faculty of Science and Technology, Government College University Faisalabad, Li, Xin, Masood, Muqaddas, Yang, Guang, Wang, Na, Wei, Wei, Dental Hospital, Jilin Universities, Changchun 130021, He, Xi, Watanabe, Nobumoto, Li, Jiang, & Li, Xiaomeng. CD147-induced cell proliferation is associated with Smad4 signal inhibition. United States. doi:10.1016/J.YEXCR.2017.07.003.
Qin, Hui, Rasul, Azhar, Bio-Active Compounds Discovery Research Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Department of Zoology, Faculty of Science and Technology, Government College University Faisalabad, Li, Xin, Masood, Muqaddas, Yang, Guang, Wang, Na, Wei, Wei, Dental Hospital, Jilin Universities, Changchun 130021, He, Xi, Watanabe, Nobumoto, Li, Jiang, and Li, Xiaomeng. Fri . "CD147-induced cell proliferation is associated with Smad4 signal inhibition". United States. doi:10.1016/J.YEXCR.2017.07.003.
@article{osti_22738158,
title = {CD147-induced cell proliferation is associated with Smad4 signal inhibition},
author = {Qin, Hui and Rasul, Azhar and Bio-Active Compounds Discovery Research Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198 and Department of Zoology, Faculty of Science and Technology, Government College University Faisalabad and Li, Xin and Masood, Muqaddas and Yang, Guang and Wang, Na and Wei, Wei and Dental Hospital, Jilin Universities, Changchun 130021 and He, Xi and Watanabe, Nobumoto and Li, Jiang and Li, Xiaomeng},
abstractNote = {CD147 is a multifunctional trans-membrane glycoprotein, which is highly expressed in many cancers. However, the mechanism by which CD147 modulates cell proliferation is not fully understood. The aim of this study is to investigate the role of CD147 in cell proliferation associated with the TGF-β/Smad4 signaling pathway. Here, we used cell viability and clone formation assays in LNCaP prostate cancer cells to demonstrate that CD147 promotes cell proliferation. The luciferase assay and western blotting show that silencing CD147 using shRNA enhances transcription and expression of p21{sup WAF1}. Using immunofluorescence and nuclear-cytoplasmic separation, we show that this is primarily attributed to transport of Smad4 from the cytoplasm to nucleus. Other assays (GST pull-down, co-immunoprecipitation and immunofluorescence) demonstrate that Smad4 is a new interaction partner of CD147, with the Smad4 MH2 domain and CD147 intracellular domain (CD147-ICD) being involved in the interaction. Furthermore, we report that a phosphoserine (pSer) in CD147 (pSer252) is responsible for this interaction and inhibition of the Smad4/p21{sup WAF1} signal that promotes cell proliferation. Our results provide a novel molecular mechanism for CD147-induced cell proliferation associated with Smad4 signal inhibition. - Highlights: • Smad4 interacts with CD147 via the MH2 domain. • CD147 prevents Smad4 translocation into the nuclear to regulate p21 transcription. • CD147 inhibits p21 transcription and expression independent on p53. • pCD147-S252 is responsible for interaction with Smad4 and p21 down-regulation.},
doi = {10.1016/J.YEXCR.2017.07.003},
journal = {Experimental Cell Research},
issn = {0014-4827},
number = 2,
volume = 358,
place = {United States},
year = {2017},
month = {9}
}