TY - JOUR
T1 - PODXL2 maintains cellular stemness and promotes breast cancer development through the Rac1/Akt pathway
AU - Lin, Yi Yi
AU - Wang, Chih Yang
AU - Phan, Nam Nhut
AU - Chiao, Chung Chieh
AU - Li, Chung Yen
AU - Sun, Zhengda
AU - Hung, Jui Hsiang
AU - Chen, Yi Ling
AU - Yen, Meng Chi
AU - Weng, Tzu Yang
AU - Hsu, Hui Ping
AU - Lai, Ming Derg
N1 - Funding Information:
Bioinformatics analyses and data mining were conducted at the Bioinformatics Core at National Cheng Kung University (Tainan, Taiwan). The authors are grateful for the support from the Human Biobank, Research Center of Clinical Medicine, National Cheng Kung University Hospital. The authors give special thanks for Dr. Dan Chamberlin of his professional English editing from the office of research and development in Taipei Medical University.
Funding Information:
The study was supported by the Ministry of Science and Technology (MOST) of Taiwan (grants MOST105-2325-B-006-003 to M-D.L., MOST 108-2314-B-006-082 to H-P.H., and MOST109-2320-B-038-009-MY2 to C-Y.W.), National Cheng Kung University Hospital (grant NCKUH-10601002 to M-D.L. and NCKUH10902031 to H-P.H.), and Taipei Medical University (grant TMU-108-AE1-B16 to C-Y.W.).
PY - 2020
Y1 - 2020
N2 - The cluster of differentiation 34 (CD34) family, which includes CD34, podocalyxin-like protein 1 (PODXL), and PODXL2, are type-I transmembrane sialomucins and markers of hematopoietic stem cells (HSCs) and vascular-associated tissues. CD34 family proteins are expressed by endothelial cells and hematopoietic precursors. PODXL is well known to be associated with invadopodia formation and to promote the epithelial-mesenchymal transition, tumor migration and invasion. PODXL expression was correlated with poor survival of cancer patients. However, the role of PODXL2 in cancer has been less fully explored. To reveal the novel role of PODXL2 in breast cancer, the present study evaluated PODXL2 levels in relation to clinical outcomes of cancer patients by performing a bioinformatics analysis using the Oncomine database, Kaplan-Meier plots, and the CCLE database. Empirical validation of bioinformatics predictions was conducted utilizing the short hairpin (sh)-RNA silencing method for PODXL2 in the BT474 invasive ductal breast carcinoma cell line. The bioinformatics analysis revealed that PODXL2 overexpression was correlated with poor survival of breast cancer patients, suggesting an oncogenic role of PODXL2 in breast carcinoma. In a validation experiment, knockdown of PODXL2 in BT474 cells slightly influenced cell proliferation, suppressed migration, and inhibited expressions of downstream molecules, including Ras-related C3 botulinum toxin substrate 1 (Rac1), phosphorylated (p)-Akt (S473), and p-paxillin (Y31) proteins. In addition, knockdown of PODXL2 reduced expression levels of cancer stem cell (CSC) markers, including Oct-4 and Nanog, and the breast CSC marker aldehyde dehydrogenase 1 (ALDH1). Collectively, our present study demonstrated that PODXL2 plays a crucial role in cancer development and could serve as a potential prognostic biomarker in breast cancer patients.
AB - The cluster of differentiation 34 (CD34) family, which includes CD34, podocalyxin-like protein 1 (PODXL), and PODXL2, are type-I transmembrane sialomucins and markers of hematopoietic stem cells (HSCs) and vascular-associated tissues. CD34 family proteins are expressed by endothelial cells and hematopoietic precursors. PODXL is well known to be associated with invadopodia formation and to promote the epithelial-mesenchymal transition, tumor migration and invasion. PODXL expression was correlated with poor survival of cancer patients. However, the role of PODXL2 in cancer has been less fully explored. To reveal the novel role of PODXL2 in breast cancer, the present study evaluated PODXL2 levels in relation to clinical outcomes of cancer patients by performing a bioinformatics analysis using the Oncomine database, Kaplan-Meier plots, and the CCLE database. Empirical validation of bioinformatics predictions was conducted utilizing the short hairpin (sh)-RNA silencing method for PODXL2 in the BT474 invasive ductal breast carcinoma cell line. The bioinformatics analysis revealed that PODXL2 overexpression was correlated with poor survival of breast cancer patients, suggesting an oncogenic role of PODXL2 in breast carcinoma. In a validation experiment, knockdown of PODXL2 in BT474 cells slightly influenced cell proliferation, suppressed migration, and inhibited expressions of downstream molecules, including Ras-related C3 botulinum toxin substrate 1 (Rac1), phosphorylated (p)-Akt (S473), and p-paxillin (Y31) proteins. In addition, knockdown of PODXL2 reduced expression levels of cancer stem cell (CSC) markers, including Oct-4 and Nanog, and the breast CSC marker aldehyde dehydrogenase 1 (ALDH1). Collectively, our present study demonstrated that PODXL2 plays a crucial role in cancer development and could serve as a potential prognostic biomarker in breast cancer patients.
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UR - http://www.scopus.com/inward/citedby.url?scp=85087810571&partnerID=8YFLogxK
U2 - 10.7150/ijms.46125
DO - 10.7150/ijms.46125
M3 - Article
C2 - 32669966
AN - SCOPUS:85087810571
VL - 17
SP - 1639
EP - 1651
JO - International Journal of Medical Sciences
JF - International Journal of Medical Sciences
SN - 1449-1907
IS - 11
ER -