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Cited by 250

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

Translational up-regulation of the EGFR by tumor hypoxia provides a nonmutational explanation for its overexpression in human cancer

Franovic, Aleksandra, Gunaratnam, Lakshman, Smith, Karlene, Robert, Isabelle, Patten, David, Lee, Stephen·2007·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0702387104
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Abstract

Overexpression of the EGF receptor (EGFR) is a recurrent theme in human cancer and is thought to cause aggressive phenotypes and resistance to standard therapy. There has, thus, been a concerted effort in identifying EGFR gene mutations to explain misregulation of EGFR expression as well as differential sensitivity to anti-EGFR drugs. However, such genetic alterations have proven to be rare occurrences in most types of cancer, suggesting the existence of a more general physiological trigger for aberrant EGFR expression. Here, we provide evidence that overexpression of wild-type EGFR can be induced by the hypoxic microenvironment and activation of hypoxia-inducible factor 2-α (HIF2α) in the core of solid tumors. Our data suggest that hypoxia/HIF2α activation represents a common mechanism for EGFR overexpression by increasing EGFR mRNA translation, thereby diminishing the necessity for gene mutations. This allows for the accumulation of elevated EGFR levels, increasing its availability for the autocrine signaling required for tumor cell growth autonomy. Taken together, our findings provide a nonmutational explanation for EGFR overexpression in human tumors and highlight a role for HIF2α activation in the regulation of EGFR protein synthesis.

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  • The increase in radiolabel during the 4-h chase in control cells is consistent with EGFR becoming more antibody reactive as the receptor undergoes posttranslational modification.

    “The increase in radiolabel during the 4-h chase in control cells (Fig. 5C) is consistent with the EGFR becoming more antibody reactive as the receptor undergoes posttranslational modification, as shown previously (65, 66).”

    From EHD1 and RUSC2 Control Basal Epidermal Growth Factor Receptor Cell Surface Expression and Recycling (2020) · cites this paper as [65]

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Research works printed but not linked: 35

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Metadata

Authors
Franovic, A., Gunaratnam, L., Smith, K., Robert, I., Patten, D., & Lee, S.
Affiliations
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8M5
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2007-08-07
Volume
104
Issue
32
Pages
13092-13097
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.0702387104
Cited by
250
References
4
Language
en

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