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Title: PRL3 induces polypoid giant cancer cells eliminated by PRL3-zumab to reduce tumor relapse
Authors: Thura, Min
Ye, Zu
Al-Aidaroos, Abdul Qader
Xiong, Qiancheng
Ong, Jun Yi
Gupta, Abhishek
Li, Jie
Guo, Ke
Ang, Koon Hwee
Zeng, Qi 
Issue Date: 29-Jul-2021
Publisher: Nature Research
Citation: Thura, Min, Ye, Zu, Al-Aidaroos, Abdul Qader, Xiong, Qiancheng, Ong, Jun Yi, Gupta, Abhishek, Li, Jie, Guo, Ke, Ang, Koon Hwee, Zeng, Qi (2021-07-29). PRL3 induces polypoid giant cancer cells eliminated by PRL3-zumab to reduce tumor relapse. Communications Biology 4 (1) : 923. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: PRL3, a unique oncotarget, is specifically overexpressed in 80.6% of cancers. In 2003, we reported that PRL3 promotes cell migration, invasion, and metastasis. Herein, firstly, we show that PRL3 induces Polyploid Giant Cancer Cells (PGCCs) formation. PGCCs constitute stem cell-like pools to facilitate cell survival, chemo-resistance, and tumor relapse. The correlations between PRL3 overexpression and PGCCs attributes raised possibilities that PRL3 could be involved in PGCCs formation. Secondly, we show that PRL3+ PGCCs co-express the embryonic stem cell markers SOX2 and OCT4 and arise mainly due to incomplete cytokinesis despite extensive DNA damage. Thirdly, we reveal that PRL3+ PGCCs tolerate prolonged chemotherapy-induced genotoxic stress via suppression of the pro-apoptotic ATM DNA damage-signaling pathway. Fourthly, we demonstrated PRL3-zumab, a First-in-Class humanized antibody drug against PRL3 oncotarget, could reduce tumor relapse in ‘tumor removal’ animal model. Finally, we confirmed that PGCCs were enriched in relapse tumors versus primary tumors. PRL3-zumab has been approved for Phase 2 clinical trials in Singapore, US, and China to block all solid tumors. This study further showed PRL3-zumab could potentially serve an ‘Adjuvant Immunotherapy’ after tumor removal surgery to eliminate PRL3+ PGCC stem-like cells, preventing metastasis and relapse. © 2021, The Author(s).
Source Title: Communications Biology
ISSN: 2399-3642
DOI: 10.1038/s42003-021-02449-8
Rights: Attribution 4.0 International
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