Podocalyxin-like protein 1 regulates TAZ signaling and stemness properties in colon cancer

Wen Ying Lee, Chih Chia Kuo, Bo Xing Lin, Chia Hsiung Cheng, Ku Chung Chen, Cheng Wei Lin

研究成果: 雜誌貢獻文章

3 引文 (Scopus)

摘要

Colon cancer is the third most common cancer in the world and the second most common cause of cancer-related mortality. Molecular biomarkers for colon cancer have undergone vigorous discovery and validation. Recent studies reported that overexpression of podocalyxin-like protein 1 (PODXL) is associated with distant metastasis and poor prognosis across several types of malignancies. Its role and underlying molecular mechanism, however, are not yet fully understood. In the present study, we revealed that the Hippo transducer, the transcriptional coactivator with PDZ-binding motif (TAZ), acts as a downstream mediator of PODXL in colon cancer. Inhibition of PODXL resulted in the suppression of TAZ signaling and the downregulation of Hippo downstream genes. Moreover, PODXL plays a critical role in cancer stemness, invasiveness, and sensitivity to chemotherapies in colon cancer HCT15 cells. Notably, expression of PODXL showed a positive correlation with stem-like and epithelial-mesenchymal transition (EMT) core signatures, and was associated with poor survival outcomes in patients with colon cancer. These findings provide novel insights into the molecular mechanism of PODXL-mediated tumorigenesis in colon cancer.

原文英語
文章編號2047
期刊International Journal of Molecular Sciences
18
發行號10
DOIs
出版狀態已發佈 - 十月 1 2017

指紋

Colonic Neoplasms
cancer
proteins
Proteins
Neoplasms
Epithelial-Mesenchymal Transition
Chemotherapy
Biomarkers
Transducers
podocalyxin
Carcinogenesis
Down-Regulation
prognosis
Genes
mortality
biomarkers
metastasis
chemotherapy
Neoplasm Metastasis
stems

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

引用此文

Podocalyxin-like protein 1 regulates TAZ signaling and stemness properties in colon cancer. / Lee, Wen Ying; Kuo, Chih Chia; Lin, Bo Xing; Cheng, Chia Hsiung; Chen, Ku Chung; Lin, Cheng Wei.

於: International Journal of Molecular Sciences, 卷 18, 編號 10, 2047, 01.10.2017.

研究成果: 雜誌貢獻文章

@article{4f75e6804ff04cea9fab346667b6060c,
title = "Podocalyxin-like protein 1 regulates TAZ signaling and stemness properties in colon cancer",
abstract = "Colon cancer is the third most common cancer in the world and the second most common cause of cancer-related mortality. Molecular biomarkers for colon cancer have undergone vigorous discovery and validation. Recent studies reported that overexpression of podocalyxin-like protein 1 (PODXL) is associated with distant metastasis and poor prognosis across several types of malignancies. Its role and underlying molecular mechanism, however, are not yet fully understood. In the present study, we revealed that the Hippo transducer, the transcriptional coactivator with PDZ-binding motif (TAZ), acts as a downstream mediator of PODXL in colon cancer. Inhibition of PODXL resulted in the suppression of TAZ signaling and the downregulation of Hippo downstream genes. Moreover, PODXL plays a critical role in cancer stemness, invasiveness, and sensitivity to chemotherapies in colon cancer HCT15 cells. Notably, expression of PODXL showed a positive correlation with stem-like and epithelial-mesenchymal transition (EMT) core signatures, and was associated with poor survival outcomes in patients with colon cancer. These findings provide novel insights into the molecular mechanism of PODXL-mediated tumorigenesis in colon cancer.",
keywords = "Cancer stem cells, Colon cancer, Epithelial-mesenchymal transition, Podocalyxin, TAZ",
author = "Lee, {Wen Ying} and Kuo, {Chih Chia} and Lin, {Bo Xing} and Cheng, {Chia Hsiung} and Chen, {Ku Chung} and Lin, {Cheng Wei}",
year = "2017",
month = "10",
day = "1",
doi = "10.3390/ijms18102047",
language = "English",
volume = "18",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "10",

}

TY - JOUR

T1 - Podocalyxin-like protein 1 regulates TAZ signaling and stemness properties in colon cancer

AU - Lee, Wen Ying

AU - Kuo, Chih Chia

AU - Lin, Bo Xing

AU - Cheng, Chia Hsiung

AU - Chen, Ku Chung

AU - Lin, Cheng Wei

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Colon cancer is the third most common cancer in the world and the second most common cause of cancer-related mortality. Molecular biomarkers for colon cancer have undergone vigorous discovery and validation. Recent studies reported that overexpression of podocalyxin-like protein 1 (PODXL) is associated with distant metastasis and poor prognosis across several types of malignancies. Its role and underlying molecular mechanism, however, are not yet fully understood. In the present study, we revealed that the Hippo transducer, the transcriptional coactivator with PDZ-binding motif (TAZ), acts as a downstream mediator of PODXL in colon cancer. Inhibition of PODXL resulted in the suppression of TAZ signaling and the downregulation of Hippo downstream genes. Moreover, PODXL plays a critical role in cancer stemness, invasiveness, and sensitivity to chemotherapies in colon cancer HCT15 cells. Notably, expression of PODXL showed a positive correlation with stem-like and epithelial-mesenchymal transition (EMT) core signatures, and was associated with poor survival outcomes in patients with colon cancer. These findings provide novel insights into the molecular mechanism of PODXL-mediated tumorigenesis in colon cancer.

AB - Colon cancer is the third most common cancer in the world and the second most common cause of cancer-related mortality. Molecular biomarkers for colon cancer have undergone vigorous discovery and validation. Recent studies reported that overexpression of podocalyxin-like protein 1 (PODXL) is associated with distant metastasis and poor prognosis across several types of malignancies. Its role and underlying molecular mechanism, however, are not yet fully understood. In the present study, we revealed that the Hippo transducer, the transcriptional coactivator with PDZ-binding motif (TAZ), acts as a downstream mediator of PODXL in colon cancer. Inhibition of PODXL resulted in the suppression of TAZ signaling and the downregulation of Hippo downstream genes. Moreover, PODXL plays a critical role in cancer stemness, invasiveness, and sensitivity to chemotherapies in colon cancer HCT15 cells. Notably, expression of PODXL showed a positive correlation with stem-like and epithelial-mesenchymal transition (EMT) core signatures, and was associated with poor survival outcomes in patients with colon cancer. These findings provide novel insights into the molecular mechanism of PODXL-mediated tumorigenesis in colon cancer.

KW - Cancer stem cells

KW - Colon cancer

KW - Epithelial-mesenchymal transition

KW - Podocalyxin

KW - TAZ

UR - http://www.scopus.com/inward/record.url?scp=85030096076&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030096076&partnerID=8YFLogxK

U2 - 10.3390/ijms18102047

DO - 10.3390/ijms18102047

M3 - Article

AN - SCOPUS:85030096076

VL - 18

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 10

M1 - 2047

ER -