@article{47b126405b3c450ea3de4e340c95e8d7,
title = "PODXL2 maintains cellular stemness and promotes breast cancer development through the Rac1/Akt pathway",
abstract = "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.",
keywords = "Bioinformatics, Breast cancer, Cancer stem cells, PODXL2",
author = "Lin, {Yi Yi} and Wang, {Chih Yang} and Phan, {Nam Nhut} and Chiao, {Chung Chieh} and Li, {Chung Yen} and Zhengda Sun and Hung, {Jui Hsiang} and Chen, {Yi Ling} and Yen, {Meng Chi} and Weng, {Tzu Yang} and Hsu, {Hui Ping} and Lai, {Ming Derg}",
note = "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.). 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.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.). 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. Publisher Copyright: {\textcopyright} The author(s).",
year = "2020",
doi = "10.7150/ijms.46125",
language = "English",
volume = "17",
pages = "1639--1651",
journal = "International Journal of Medical Sciences",
issn = "1449-1907",
publisher = "Ivyspring International Publisher",
number = "11",
}
