Blog
About

54
views
0
recommends
+1 Recommend
0
shares
  • Review: found
Is Open Access

Review of 'EGF/EGFR signaling axis is a significant regulator of the proteasome expression and activity in colon cancer cells'

Bookmark
3
The present study is interesting, but has some defects.
Average rating:
    Rated 3 of 5.
Level of importance:
    Rated 3 of 5.
Level of validity:
    Rated 3 of 5.
Level of completeness:
    Rated 2 of 5.
Level of comprehensibility:
    Rated 3 of 5.
Competing interests:
None

Reviewed article

  • Record: found
  • Abstract: found
  • Article: found
Is Open Access

EGF/EGFR signaling axis is a significant regulator of the proteasome expression and activity in colon cancer cells

(2014)
Colon cancer is the third most common type of cancer worldwide. Epidermal growth factor receptor (EGFR) plays a crucial role in the (patho)physiology of the disease. EGFR controls vital cellular processes, while this action is associated with poor prognosis. In addition, K-Ras mutations are associated with the promotion of the disease and the anti-EGFR resistance. The ubiquitin-proteasome system plays also a very important role in cancer, modulating cell cycle and other cellular processes such as the growth and the survival of cancer cells. Proteasome inhibition affects, in several cases, the action and the protein levels of EGFR. Nevertheless, little is known whether the reversed option is possible. In this study, we, therefore, investigated the impact of epidermal growth factor (EGF)/EGFR signaling axis on gene expression and the proteolytic activity of the proteasome subunits, as well as whether Nrf2, an activator of proteasome expression, plays a role in this process. Moreover, we evaluated whether EGF regulates the expression of its own receptor and the proliferation rate of DLD-1 (K-Ras mutated) colon cancer cells. The obtained data showed that, although EGF has no significant effect on the proliferation of DLD-1 colon cancer cells, it significantly upregulates the expression of EGFR as well as the expression and the activity of the proteasome, suggesting that the EGF-mediated proteasome activation could possibly lead to enhanced EGFR degradation leading to autoregulation of EGF–EGFR pathway. Nrf2 activation did not induce proteasome gene expression in DLD-1 colon cancer cells.
    Bookmark

    Review information

    10.14293/S2199-1006.1.SOR-LIFE.AAC0E6.v1.RGMWVR

    This work has been published open access under Creative Commons Attribution License CC BY 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com.

    Review text

    I think that the present study entitled “EGF/EGFR signaling axis is as significant regulator of the proteasome expression and activity in colon cancer cells” is interesting, but has some defects and a bizarre and fanciful section in Discussion section.

    The authors investigated the effects of EGF on mRNA expression levels of EGFR and proteasome subunits and activities of proteasome beta 5 subunits, and cell proliferation in K-ras mutant (DLD-1) colon cancer cells using RT-PCR and quantitative PCR, and fluorogenic substrate assay, and WST-1 assay, respectively.
    EGF up-regulated the expression levels of EGFR and proteasome beta subunits including beta 1, 2, and 5, and activities of beta 5 subunits. AG1478 significantly abrogated these effects, but CP-724/714 did not. EGF did not promote cell proliferation in K-ras mutated cells. Oltipaz as a Nrf2 synthetic activator did not affect the expression levels of proteasome beta subunits. The authors concluded that EGF/EGFR signaling axis is as significant regulator of the proteasome expression and activity in colon cancer cells


    Major
    1. Introduction section is too long. Please describe concisely and succinctly.

    2. In Discussion section and conclusion, authors speculated that EGF does not affect the proliferation of DLD-1 cells, possibly due to the enhanced proteolytic action of proteasome on EGFR.
    This is a bizarre and fanciful speculation.
    The K-ras mutations are considered to lead continuous activation of its downstream pathways.
    Are the expression levels of EGFR in DLD-1 cells lower than those in K-ras wild cells due to proteolysis of EGFR? Please show whether expression levels of EGFR in DLD-1 cells are significantly low, compared with wild cells. In addition, please show how EGFR degradation by proteasomes induce cell survival.

    Comments

    Comment on this review