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

  • Authors:
    • Tiia Honkanen
    • Emmi Wilenius
    • Peppi Koivunen
    • Jussi P. Koivunen
  • View Affiliations

  • Published online on: June 21, 2017     https://doi.org/10.3892/ijo.2017.4048
  • Pages:599-606
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Abstract

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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August 2017
Volume 51 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
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APA
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. https://doi.org/10.3892/ijo.2017.4048
MLA
Honkanen, T., Wilenius, E., Koivunen, P., Koivunen, J. P."HER2 regulates cancer stem-like cell phenotype in ALK translocated NSCLC". International Journal of Oncology 51.2 (2017): 599-606.
Chicago
Honkanen, T., Wilenius, E., Koivunen, P., Koivunen, J. P."HER2 regulates cancer stem-like cell phenotype in ALK translocated NSCLC". International Journal of Oncology 51, no. 2 (2017): 599-606. https://doi.org/10.3892/ijo.2017.4048