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Int J Mol Sci. 2017 Sep 23;18(10). pii: E2047. doi: 10.3390/ijms18102047.

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

Lee WY1,2, Kuo CC3,4, Lin BX5,6, Cheng CH7,8, Chen KC9,10, Lin CW11,12,13.

Author information

1
Department of Cytopathology, Chi Mei Medical Center, Tainan 710, Taiwan. d940232@mail.chimei.org.tw.
2
Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. d940232@mail.chimei.org.tw.
3
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. b507101052@tmu.edu.tw.
4
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. b507101052@tmu.edu.tw.
5
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. xzx22668844@gmail.com.
6
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. xzx22668844@gmail.com.
7
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. chcheng@tmu.edu.tw.
8
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. chcheng@tmu.edu.tw.
9
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. kuchung@tmu.edu.tw.
10
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. kuchung@tmu.edu.tw.
11
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. cwlin@tmu.edu.tw.
12
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. cwlin@tmu.edu.tw.
13
Center for Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei 110, Taiwan. cwlin@tmu.edu.tw.

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:

TAZ; cancer stem cells; colon cancer; epithelial-mesenchymal transition; podocalyxin

PMID:
28946619
PMCID:
PMC5666729
DOI:
10.3390/ijms18102047
[Indexed for MEDLINE]
Free PMC Article

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