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Int. J. Mol. Sci. 2017, 18(10), 2047; doi:10.3390/ijms18102047

Podocalyxin-Like Protein 1 Regulates TAZ Signaling and Stemness Properties in Colon Cancer

1
Department of Cytopathology, Chi Mei Medical Center, Tainan 710, Taiwan
2
Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
3
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
4
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
5
Center for Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei 110, Taiwan
*
Author to whom correspondence should be addressed.
Received: 9 August 2017 / Revised: 16 September 2017 / Accepted: 19 September 2017 / Published: 23 September 2017
(This article belongs to the Special Issue Cancer Stem Cells)
View Full-Text   |   Download PDF [3395 KB, uploaded 23 September 2017]   |  

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. View Full-Text
Keywords: colon cancer; epithelial-mesenchymal transition; podocalyxin; TAZ; cancer stem cells colon cancer; epithelial-mesenchymal transition; podocalyxin; TAZ; cancer stem cells
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MDPI and ACS Style

Lee, W.-Y.; Kuo, C.-C.; Lin, B.-X.; Cheng, C.-H.; Chen, K.-C.; Lin, C.-W. Podocalyxin-Like Protein 1 Regulates TAZ Signaling and Stemness Properties in Colon Cancer. Int. J. Mol. Sci. 2017, 18, 2047.

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