Identification of the Novel Role of CD24 as an Oncogenesis Regulator and Therapeutic Target for Triple-Negative Breast Cancer
Authors: King-Jen Chang
Shih Sheng Jiang
Wen-Hung Kuo
Shu-Yi Chiu
Wen-Chun Hung
Lu-Hai Wang
Heng-Yi Chen
Kuo-Wang Tsai
Shih-Hsuan Chan
Journal: Molecular Cancer Therapeutics (2019)
Discipline: CLINICAL MEDICINE
Keywords: Triple-negative breast cancer; CD24; metastasis; lymphangiogenesis; angiogenesis
Affiliations: Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan., Institute of Molecular and Medicine, National Tsing Hua University, Hsinchu, Taiwan., Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan., Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan., Department of Chemical Biology, National Pingtung University of Education, Pingtung, Taiwan., Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan., Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan., National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan., Department of Surgery, Taiwan Adventist Hospital, Taipei, Taiwan., National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan., Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. ., Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.

Abstract:  Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, with unfavorable prognosis and 5-year survival. The purpose of this study was to investigate the underlying mechanisms involved in TNBC progression. We determined that CD24 expression was elevated in highly lung and lymph node metastatic TNBC cells. CD24 depletion inhibited primary tumor growth and lymph node and lung metastasis and reduced the number of blood and lymphatic vessels in the tumor microenvironment. CD24 knockdown impaired EGFR/Met-mediated signaling and reduced lymphangiogenesis- and angiogenesis-related molecules, including vascular endothelial growth factors A and C, by promoting EGFR and Met protein instability via the lysosomal degradation pathway. CD24 monoclonal antibody treatment reduced lung metastasis and prolonged the survival in a lung metastasis mouse model. Clinical analyses revealed that the CD24 high/MET high "double-positive" signature identified a subset of TNBC patients with worst outcomes. We conclude that CD24 could be a therapeutic target by itself and in combination with the Met expression could be a good prognostic biomarker for TNBC patients. 

Retracted: No

PubPeer comments:
 ![file] , 
 Prior to the notice on Pubpeer, we had noticed this mistake earlier and had already contacted the journal to make an erratum note on June 18, 2020 and the correction process is already underway. (see the email communication below) The original version of our MCT Article contained an error in the Figure 1A where the representative image of IV2-1 cells at the 1-hour time point was incorrect in that the same image of 231-P cells at the 1-hour time point was mis-planted inadvertently. The representative cell mobility images only served to display visually an example of the respective cells migration pattern. The quantitative data of cell mobility based on multiple cells were presented in the histograms in Fig 1B. The mistake of the mis-placed exemplified image did not change the conclusion of the quantitative data. We present here the original raw data of live migration imaging of cells to show images of each time point collected and used for 231, IV2 and LC cells (shown below). The correct image in Fig1A second row second cell migration image from the left should be the IV2-1 cells at the 1-hour time point (as indicated by the yellow square with green check mark shown in the figure below). The correct image of the IV2 cells at one hour time point is used to replace the original wrong one, and the corrected Fig. 1A has been sent to MCT to make an erratum note on June 18, 2020. We apologize for this mistake in assembling the cell migration images for Fig.1A in the original paper. Messages to MCT for correction --------- Original Message --------- From: u738bu9678u6d77 luhaiwang@mail.cmu.edu.tw To: meredith.kahn@aacr.org Cc: Shi-Hsuan jamesgeography@gmail.com Sent: 2020 06 18 13:15 Subject: correction of our MCT paperu5bc4u4ef6u4eba: u738bu9678u6d77 u6536u4ef6u4eba: mct@aacr.org; We are writing to you to correct two inadvertent errors in our published MCT paper entitled u201cIdentification of the novel role of CD24 as an oncogenesis regulator and therapeutic target for Triple Negative Breast Canceru201d (Mol Cancer Ther 2019, 18(1):147-161.). As the corresponding author of the paper, I am writing to ask MCT to make an erratum note of the two errors. The correction does not change any of the conclusions of the paper. We sincerely apologize for those inadvertent mistakes and the inconvenience that have caused. The original version of this Article contained an error in the Figure 1A where the representative images of IV2-1 cells at the 1-hour time point was incorrect in that the same image of 231-P cells at the 1-hour time point was mis-planted inadvertently. The correct image should be the IV2-1 cells at the 1-hour time point. The correct image is now used to replace the original wrong one. This error has been corrected in Figure 1A. From:  Kahn, Meredith meredith.kahn@aacr.org To: u738bu9678u6d77 luhaiwang@mail.cmu.edu.tw Sent: 2020 06 18 13:21 Subject: Automatic reply: correction of our MCT paper Meredith Kahn, is no longer an employee at AACR. Please address your future emails to mct@aacr.org. Please do not reply to this email. We are unable to respond to messages sent in reply to this email. Shih-Hsuan Chan, Ph.D. (First Author) Project Assistant Professor Graduate Institute of Integrated Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung, 40402, Taiwan, R. O. C. E-mail: jamesc27@mail.cmu.edu.tw TEL: 886 4-22053366 ext:3510 Lu-Hai Wang, Ph.D. (Corresponding Author) Chair Professor Graduate Institute of Integrated Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung, 40402, Taiwan, R. O. C. E-mail: luhaiwang@mail.cmu.edu.tw TEL: 886 4 22057153 ![file] ,