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World J Clin Oncol. Dec 10, 2014; 5(5): 806-823
Published online Dec 10, 2014. doi: 10.5306/wjco.v5.i5.806
Nexus of signaling and endocytosis in oncogenesis driven by non-small cell lung cancer-associated epidermal growth factor receptor mutants
Byung Min Chung, Eric Tom, Neha Zutshi, Timothy Alan Bielecki, Vimla Band, Hamid Band
Byung Min Chung, Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Johns Hopkins University, Baltimore, MD 21205, United States
Eric Tom, Neha Zutshi, Timothy Alan Bielecki, Vimla Band, Hamid Band, Eppley Institute for Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, United States
Eric Tom, Neha Zutshi, Hamid Band, Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-6805, United States
Neha Zutshi, Hamid Band, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-6805, United States
Vimla Band, Hamid Band, Department of Genetics, Cell Biology and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-6805, United States
Vimla Band, Hamid Band, Department of Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198-6805, United States
Author contributions: All the authors contributed to this paper.
Supported by the NIH grant to Band H, No. CA99163, CA87986, CA105489 and CA116552; a Department of Defense grant to Band H, No. W81WH-11-1-0167; the NIH grant to Band V, No. CA96844 and CA144027; and Department of Defense grant to Band V, No. W81XWH-07-1-0351 and W81XWH-11-1-0171; the Nebraska Department of Health and Human Services LB-506 grant to Band H, No. 2014-01; and the NCI Core Support Grant to the UNMC Buffett Cancer Center; Bielecki TA was a predoctoral trainee under the NCI Institutional Cancer Biology Training Grant, No. CA009476
Correspondence to: Hamid Band, MD, PhD, Elizabeth Bruce Professor of Cancer Research, Eppley Institute for Cancer and Allied Diseases, University of Nebraska Medical Center, 4400 Emile St, Omaha, NE 68198-6805, United States. hband@unmc.edu
Telephone: +1-402-5598572
Received: May 22, 2014
Revised: July 19, 2014
Accepted: September 6, 2014
Published online: December 10, 2014
Core Tip

Core tip: Since their discovery ten years ago, much work has revealed the signaling properties of non-small cell lung cancer-associated mutant epidermal growth factor receptors (EGFRs). While therapeutic options for patients harboring mutants have emerged, these are beset with rapid development of resistance, making it critical that mutant EGFR biology be better understood to design more effective therapies. Emerging data suggests that mutant EGFRs exhibit altered endocytic trafficking, a process critical for the regulation of EGFR signaling. Deregulated endocytic traffic appears to enable mutant EGFRs to activate oncogenic signaling pathways. This review highlights the signaling and endocytic trafficking of mutant EGFR and the intimate link between the two processes.