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Title: P44/WDR77 restricts the sensitivity of proliferating cells to TGFβ signaling

Abstract

Highlights: • P44/WDR77 causes proliferating cells to become non-responsive to TGFβ signaling. • P44/WDR77 down-regulates TβRII and TβR2 expression. • P44/WDR77 down-regulated TGFβ signaling correlates with lung tumorigenesis. - Abstract: We previously reported that a novel WD-40 domain-containing protein, p44/WDR77, drives quiescent epithelial cells to re-enter the cell cycle and plays an essential role for growth of lung and prostate cancer cells. Transforming growth factor beta (TGFβ) signaling is important in the maintenance of non-transformed cells in the quiescent or slowly cycling stage. However, both non-transformed proliferating cells and human cancer cells are non-responsive to endogenous TGFβ signaling. The mechanism by which proliferating cells become refractory to TGFβ inhibition is not well established. Here, we found that silencing p44/WDR77 increased cellular sensitivity to TGFβ signaling and that this was inversely correlated with decreased cell proliferation. Smad2 or 3 phosphorylation, TGFβ-mediated transcription, and TGFβ2 and TGFβ receptor type II (TβRII) expression were dramatically induced by silencing of p44/WDR77. These data support the hypothesis that p44/WDR77 down-regulates the expression of the TGFβ ligand and its receptor, thereby leading to a cellular non-response to TGFβ signaling. Finally, we found that p44/WDR77 expression was correlated with cell proliferation and decreased TGFβ signaling during lungmore » tumorigenesis. Together, these results suggest that p44/WDR77 expression causes the non-sensitivity of proliferating cells to TGFβ signaling, thereby contributing to cellular proliferation during lung tumorigenesis.« less

Authors:
 [1];  [2];  [3];  [4];  [2];  [1];  [3]
  1. Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, Hubei 430022 (China)
  2. (United States)
  3. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States)
  4. Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038 (China)
Publication Date:
OSTI Identifier:
22416636
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 450; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL CYCLE; CELL PROLIFERATION; GROWTH FACTORS; HUMAN POPULATIONS; INHIBITION; LIGANDS; LUNGS; MAINTENANCE; NEOPLASMS; PHOSPHORYLATION; PROSTATE; RECEPTORS; SENSITIVITY; TRANSCRIPTION

Citation Formats

Yi, Pengfei, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, Gao, Shen, Gu, Zhongping, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, Huang, Tao, and Wang, Zhengxin, E-mail: zhenwang@mdanderson.org. P44/WDR77 restricts the sensitivity of proliferating cells to TGFβ signaling. United States: N. p., 2014. Web. doi:10.1016/J.BBRC.2014.05.125.
Yi, Pengfei, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, Gao, Shen, Gu, Zhongping, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, Huang, Tao, & Wang, Zhengxin, E-mail: zhenwang@mdanderson.org. P44/WDR77 restricts the sensitivity of proliferating cells to TGFβ signaling. United States. doi:10.1016/J.BBRC.2014.05.125.
Yi, Pengfei, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, Gao, Shen, Gu, Zhongping, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, Huang, Tao, and Wang, Zhengxin, E-mail: zhenwang@mdanderson.org. Fri . "P44/WDR77 restricts the sensitivity of proliferating cells to TGFβ signaling". United States. doi:10.1016/J.BBRC.2014.05.125.
@article{osti_22416636,
title = {P44/WDR77 restricts the sensitivity of proliferating cells to TGFβ signaling},
author = {Yi, Pengfei and Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 and Gao, Shen and Gu, Zhongping and Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 and Huang, Tao and Wang, Zhengxin, E-mail: zhenwang@mdanderson.org},
abstractNote = {Highlights: • P44/WDR77 causes proliferating cells to become non-responsive to TGFβ signaling. • P44/WDR77 down-regulates TβRII and TβR2 expression. • P44/WDR77 down-regulated TGFβ signaling correlates with lung tumorigenesis. - Abstract: We previously reported that a novel WD-40 domain-containing protein, p44/WDR77, drives quiescent epithelial cells to re-enter the cell cycle and plays an essential role for growth of lung and prostate cancer cells. Transforming growth factor beta (TGFβ) signaling is important in the maintenance of non-transformed cells in the quiescent or slowly cycling stage. However, both non-transformed proliferating cells and human cancer cells are non-responsive to endogenous TGFβ signaling. The mechanism by which proliferating cells become refractory to TGFβ inhibition is not well established. Here, we found that silencing p44/WDR77 increased cellular sensitivity to TGFβ signaling and that this was inversely correlated with decreased cell proliferation. Smad2 or 3 phosphorylation, TGFβ-mediated transcription, and TGFβ2 and TGFβ receptor type II (TβRII) expression were dramatically induced by silencing of p44/WDR77. These data support the hypothesis that p44/WDR77 down-regulates the expression of the TGFβ ligand and its receptor, thereby leading to a cellular non-response to TGFβ signaling. Finally, we found that p44/WDR77 expression was correlated with cell proliferation and decreased TGFβ signaling during lung tumorigenesis. Together, these results suggest that p44/WDR77 expression causes the non-sensitivity of proliferating cells to TGFβ signaling, thereby contributing to cellular proliferation during lung tumorigenesis.},
doi = {10.1016/J.BBRC.2014.05.125},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 450,
place = {United States},
year = {Fri Jul 18 00:00:00 EDT 2014},
month = {Fri Jul 18 00:00:00 EDT 2014}
}