Podocalyxin-Like Protein 1 Regulates TAZ Signaling and Stemness Properties in Colon Cancer
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 associa...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/18/10/2047 |
| _version_ | 1811315508873527296 |
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| author | Wen-Ying Lee Chih-Chia Kuo Bo-Xing Lin Chia-Hsiung Cheng Ku-Chung Chen Cheng-Wei Lin |
| author_facet | Wen-Ying Lee Chih-Chia Kuo Bo-Xing Lin Chia-Hsiung Cheng Ku-Chung Chen Cheng-Wei Lin |
| author_sort | Wen-Ying Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T11:31:28Z |
| format | Article |
| id | doaj.art-10f17cef92cf4df7a9ba06e09a569092 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T11:31:28Z |
| publishDate | 2017-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-10f17cef92cf4df7a9ba06e09a5690922022-12-22T02:48:33ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-09-011810204710.3390/ijms18102047ijms18102047Podocalyxin-Like Protein 1 Regulates TAZ Signaling and Stemness Properties in Colon CancerWen-Ying Lee0Chih-Chia Kuo1Bo-Xing Lin2Chia-Hsiung Cheng3Ku-Chung Chen4Cheng-Wei Lin5Department of Cytopathology, Chi Mei Medical Center, Tainan 710, TaiwanDepartment of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, TaiwanDepartment of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, TaiwanDepartment of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, TaiwanDepartment of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, TaiwanDepartment of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, TaiwanColon 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.https://www.mdpi.com/1422-0067/18/10/2047colon cancerepithelial-mesenchymal transitionpodocalyxinTAZcancer stem cells |
| spellingShingle | Wen-Ying Lee Chih-Chia Kuo Bo-Xing Lin Chia-Hsiung Cheng Ku-Chung Chen Cheng-Wei Lin Podocalyxin-Like Protein 1 Regulates TAZ Signaling and Stemness Properties in Colon Cancer International Journal of Molecular Sciences colon cancer epithelial-mesenchymal transition podocalyxin TAZ cancer stem cells |
| title | Podocalyxin-Like Protein 1 Regulates TAZ Signaling and Stemness Properties in Colon Cancer |
| title_full | Podocalyxin-Like Protein 1 Regulates TAZ Signaling and Stemness Properties in Colon Cancer |
| title_fullStr | Podocalyxin-Like Protein 1 Regulates TAZ Signaling and Stemness Properties in Colon Cancer |
| title_full_unstemmed | Podocalyxin-Like Protein 1 Regulates TAZ Signaling and Stemness Properties in Colon Cancer |
| title_short | Podocalyxin-Like Protein 1 Regulates TAZ Signaling and Stemness Properties in Colon Cancer |
| title_sort | podocalyxin like protein 1 regulates taz signaling and stemness properties in colon cancer |
| topic | colon cancer epithelial-mesenchymal transition podocalyxin TAZ cancer stem cells |
| url | https://www.mdpi.com/1422-0067/18/10/2047 |
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