Original Article
Volume: 4 | Issue: 1 | Published: Nov 15, 2020 | Pages: 1 - 13 | DOI: 10.24911/JBCGenetics/183-1594626414
Epidermal growth factor receptor and STAT3 signal through KRAS have mutually opposite effects on CTEN
Authors: Saleh AlGhamdi , Salih Ibrahim , Kanwal Balloch , Darryl Jackson , Mohammad Ilyas
Article Info
Authors
Saleh AlGhamdi
Department of Pathology, College of Medicine, University of Nottingham, Nottingham, United Kingdom
Salih Ibrahim
Clinical Research Department, ACRA, Research Center, King Fahad Medical City, Riyadh, Saudi Arabia
Kanwal Balloch
Department of Pathology, College of Medicine, University of Nottingham, Nottingham, United Kingdom
Darryl Jackson
Department of Biochemistry, College of Medicine, Kirkuk University, Iraq
Mohammad Ilyas
Department of Pathology, College of Medicine, University of Nottingham, Nottingham, United Kingdom
Publication History
Received: July 13, 2020
Revised: September 29, 2020
Accepted: October 04, 2020
Published: November 15, 2020
Abstract
Background: C-terminal tensin-like (CTEN) is a protein located at focal adhesions and has been reported to be an oncogene in the colon, breast, lung, and gastric cancer. In this study, we investigated whether two other proposed mechanisms, i.e., epidermal growth factor receptor (EGFR) and Signal transducer and activator of transcription 3 (STAT3) signaling were involved in regulating CTEN expression. Methodology: Initially, we manipulated EGFR signaling by (i) stimulation with epidermal growth factor (EGF) and (ii) inhibition by the PD153035 in the colorectal cancer cell lines SW620 and C32. In C32, EGF stimulation resulted in the upregulation of KRAS and CTEN, whereas exposure to PD153035 resulted in the downregulation of both KRAS and CTEN. EGFR activation and inhibition were reflected by, respectively, increased and decreased cell motility although the effect of EGFR activation was lost by CTEN knockdown. In SW620, which harbors a KRAS mutation, modulating EGFR activity in this way did not affect either KRAS or CTEN. STAT3 signaling has also been reported to positively regulate CTEN. We tested this in SW620 by directly knocking down STAT3 and exposing cells to interleukin-6 (an activator of STAT3). STAT3 knockdown resulted in increased CTEN, whereas STAT3 activation resulted in the downregulation of CTEN. Results: Testing for KRAS expression showed that STAT3 was negatively regulating KRAS, and this was reflected in the CTEN expression. Functional analysis, however, showed that the inhibition of STAT3 resulted in a reduction of cell motility in a K RAS and CTEN-independent manner. Conclusion: We conclude that both EGFR signals through KRAS to modulate CTEN (and consequently integrin- linked kinase/focal adhesion kinase) and stimulates cell motility. STAT3, however, negatively regulates KRAS and consequently CTEN although its net effect is to stimulate motility through an alternative mechanism.
Keywords: EGFR, CTEN, KRAS, STAT3, colon cancer, breast cancer
Pubmed Style
Saleh AlGhamdi, Salih Ibrahim, Kanwal Balloch, Darryl Jackson, Mohammad Ilyas. Epidermal growth factor receptor and STAT3 signal through KRAS have mutually opposite effects on CTEN. JBC Genetics. 2020; 15 (November 2020): 1-13. doi:10.24911/JBCGenetics/183-1594626414
Web Style
Saleh AlGhamdi, Salih Ibrahim, Kanwal Balloch, Darryl Jackson, Mohammad Ilyas. Epidermal growth factor receptor and STAT3 signal through KRAS have mutually opposite effects on CTEN. https://www.jbcgenetics.com/articles/2123 [Access: April 27, 2025]. doi:10.24911/JBCGenetics/183-1594626414
AMA (American Medical Association) Style
Saleh AlGhamdi, Salih Ibrahim, Kanwal Balloch, Darryl Jackson, Mohammad Ilyas. Epidermal growth factor receptor and STAT3 signal through KRAS have mutually opposite effects on CTEN. JBC Genetics. 2020; 15 (November 2020): 1-13. doi:10.24911/JBCGenetics/183-1594626414
Vancouver/ICMJE Style
Saleh AlGhamdi, Salih Ibrahim, Kanwal Balloch, Darryl Jackson, Mohammad Ilyas. Epidermal growth factor receptor and STAT3 signal through KRAS have mutually opposite effects on CTEN. JBC Genetics. (2020), [cited April 27, 2025]; 15 (November 2020): 1-13. doi:10.24911/JBCGenetics/183-1594626414
Harvard Style
Saleh AlGhamdi, Salih Ibrahim, Kanwal Balloch, Darryl Jackson, Mohammad Ilyas (2020) Epidermal growth factor receptor and STAT3 signal through KRAS have mutually opposite effects on CTEN. JBC Genetics, 15 (November 2020): 1-13. doi:10.24911/JBCGenetics/183-1594626414
Chicago Style
Saleh AlGhamdi, Salih Ibrahim, Kanwal Balloch, Darryl Jackson, Mohammad Ilyas. "Epidermal growth factor receptor and STAT3 signal through KRAS have mutually opposite effects on CTEN." 15 (2020), 1-13. doi:10.24911/JBCGenetics/183-1594626414
MLA (The Modern Language Association) Style
Saleh AlGhamdi, Salih Ibrahim, Kanwal Balloch, Darryl Jackson, Mohammad Ilyas. "Epidermal growth factor receptor and STAT3 signal through KRAS have mutually opposite effects on CTEN." 15.November 2020 (2020), 1-13. Print. doi:10.24911/JBCGenetics/183-1594626414
APA (American Psychological Association) Style
Saleh AlGhamdi, Salih Ibrahim, Kanwal Balloch, Darryl Jackson, Mohammad Ilyas (2020) Epidermal growth factor receptor and STAT3 signal through KRAS have mutually opposite effects on CTEN. , 15 (November 2020), 1-13. doi:10.24911/JBCGenetics/183-1594626414