University of Oulu

Honkanen, T., Wilenius, E., Koivunen, P., & Koivunen, J.P. (2017). HER2 regulates cancer stem-like cell phenotype in ALK translocated NSCLC. International Journal of Oncology, 51, 599-606.

HER2 regulates cancer stem-like cell phenotype in ALK translocated NSCLC

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Author: Honkanen, Tiia1,2; Wilenius, Emmi1,2; Koivunen, Peppi3,4,5;
Organizations: 1Department of Oncology and Radiotherapy, Oulu University Hospital, POB 20, 90029 OYS Oulu
2Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu
3Biocenter Oulu, POB 5000, 90014 University of Oulu
4Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu
5Oulu Center for Cell-Matrix Research, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
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Language: English
Published: Spandidos Publications, 2017
Publish Date: 2019-10-31


We have previously shown that cancer stem-like cells (CSLCs) can mediate therapy resistance in ALK translocated lung cancers. HER2 has been linked to CSLCs in breast cancers and, therefore, we wanted to assess whether HER2 has a role in CSLCs in ALK translocated cancers. ALK translocated cell lines, H3122 and H2228, with variable sensitivity to ALK inhibition were used in the study. HER2 overexpression or knockdown was induced by retro- or lentiviral infections and cells were treated with pharmacological agents targeting HER2 and ALK signaling. Furthermore, tumorigenic properties of the cells were assessed in vitro using colony and sphere formation assays. In the ALK inhibitor sensitive H3122 cells, HER2 overexpression unaltered the primary response to ALK inhibition, but increased CSLC marker expression and enhanced colony and sphere formation and late AKT and ERK1/2 signaling recovery. In the ALK inhibitor semi-sensitive H2228 cells, HER2 knockdown reduced basal expression of CSLC markers, modestly increased sensitivity to ALK inhibition in colony and sphere formation assays, and reduced late AKT and ERK1/2 signaling recovery. In addition, HER2 induced cross activation of other ErbB-members of which HER3 followed most closely the CSLC marker expression and neuregulin-1, a HER3 ligand, or pan-ErbB inhibitor afatinib, were able to alter CSLC marker expression and colony formation. the present study suggests that HER2 has an important role in the regulation of the CSLC phenotype in ALK translocated lung cancers that is mainly orchestrated by HER2/HER3 heterodimers.

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Series: International journal of oncology
ISSN: 1019-6439
ISSN-E: 1791-2423
ISSN-L: 1019-6439
Volume: 51
Issue: 2
Pages: 599 - 606
DOI: 10.3892/ijo.2017.4048
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Copyright information: © Demetrios A. Spandidos Ed. & Pub. This is the published version of an article that was published in International Journal of Oncology. The Definitive Version of Record can be found online at: