Please use this identifier to cite or link to this item:
Title: Metastasis-associated PRL-3 induces EGFR activation and addiction in cancer cells
Authors: Al-Aidaroos, A.Q.O.
Yuen, H.F.
Guo, K.
Zhang, S.D.
Chung, T.-H. 
Chng, W.J.
Zeng, Q. 
Issue Date: 1-Aug-2013
Citation: Al-Aidaroos, A.Q.O., Yuen, H.F., Guo, K., Zhang, S.D., Chung, T.-H., Chng, W.J., Zeng, Q. (2013-08-01). Metastasis-associated PRL-3 induces EGFR activation and addiction in cancer cells. Journal of Clinical Investigation 123 (8) : 3459-3471. ScholarBank@NUS Repository.
Abstract: Metastasis-associated phosphatase of regenerating liver-3 (PRL-3) has pleiotropic effects in driving cancer progression, yet the signaling mechanisms of PRL-3 are still not fully understood. Here, we provide evidence for PRL-3-induced hyperactivation of EGFR and its downstream signaling cascades in multiple human cancer cell lines. Mechanistically, PRL-3-induced activation of EGFR was attributed primarily to transcriptional downregulation of protein tyrosine phosphatase 1B (PTP1B), an inhibitory phosphatase for EGFR. Functionally, PRL-3-induced hyperactivation of EGFR correlated with increased cell growth, promigratory characteristics, and tumorigenicity. Moreover, PRL-3 induced cellular addiction to EGFR signaling, as evidenced by the pronounced reversion of these oncogenic attributes upon EGFR-specific inhibition. Of clinical significance, we verified elevated PRL-3 expression as a predictive marker for favorable therapeutic response in a heterogeneous colorectal cancer (CRC) patient cohort treated with the clinically approved anti-EGFR antibody cetuximab. The identification of PRL-3-driven EGFR hyperactivation and consequential addiction to EGFR signaling opens new avenues for inhibiting PRL-3-driven cancer progression. We propose that elevated PRL-3 expression is an important clinical predictive biomarker for favorable anti-EGFR cancer therapy.
Source Title: Journal of Clinical Investigation
ISSN: 00219738
DOI: 10.1172/JCI66824
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on May 31, 2023


checked on May 31, 2023

Page view(s)

checked on May 25, 2023

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.