Decline in arylsulfatase B (N-acetylgalactosamine-4-sulfatase) leads to increased EGFR expression due to SHP2 inhibition and JNK activation in prostate

Authors
Bhattacharyya, S.
Feferman, L.
Han, X.
Ouya, Y.
Zhang, F.
Linhardt, Robert J.
Tobacman, J.K.
ORCID
https://orcid.org/0000-0003-2219-5833
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Issue Date
2018
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Terms of Use
Attribution 3.0 United States
CC BY : this license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. Credit must be given to the authors and the original work must be properly cited.
Full Citation
Decline in arylsulfatase B (N-acetylgalactosamine-4-sulfatase) leads to increased EGFR expression due to SHP2 inhibition and JNK activation in prostate, S. Bhattacharyya, L. Feferman, X. Han, Y. Ouya, F. Zhang, R. J. Linhardt, J. K. Tobacman, Journal of Biological Chemistry, 293, 11076–11087, 2018.
Abstract
Epidermal growth factor receptor (EGFR) has a crucial role in cell differentiation and proliferation and cancer, and its expression appears to be up-regulated when arylsulfatase B (ARSB or GalNAc-4-sulfatase) is reduced. ARSB removes 4-sulfate groups from the nonreducing end of dermatan sulfate and chondroitin 4-sulfate (C4S), and its decreased expression has previously been reported to inhibit the activity of the ubiquitous protein-tyrosine phosphatase, nonreceptor type 11 (SHP2 or PTPN11). However, the mechanism by which decline in ARSB leads to decline in SHP2 activity is unclear. Here, we show that SHP2 binds preferentially C4S, rather than chondroitin 6-sulfate, and confirm that SHP2 activity declines when ARSB is silenced. The reduction in ARSB activity, and the resultant increase in C4S, increased the expression of EGFR (Her1/ErbB1) in human prostate stem and epithelial cells. The increased expression of EGFR occurred after 1) the decline in SHP2 activity, 2) enhanced c-Jun N-terminal kinase (JNK) activity, 3) increased nuclear DNA binding by c-Jun and c-Fos, and 4) EGFR promoter activation. In response to exogenous EGF, there was increased bromodeoxyuridine incorporation, consistent with enhanced cell proliferation. These findings indicated that ARSB and chondroitin 4-sulfation affect the activation of an important dual phosphorylation threonine–tyrosine kinase and the mRNA expression of a critical tyrosine kinase receptor in prostate cells. Restoration of ARSB activity with the associated reduction in C4S may provide a new therapeutic approach for managing malignancies in which EGFR-mediated tyrosine kinase signaling pathways are active.
Description
Journal of Biological Chemistry, 293, 11076–11087
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
The American Society for Biochemistry and Molecular Biology (ASBMB) and Elsevier
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
https://harc.rpi.edu/
Access
Open Access
CC BY — Creative Commons Attribution