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Editorial
. 2017 Dec;9(12):4884-4888.
doi: 10.21037/jtd.2017.11.104.

Notch signaling triggers the tumor heterogeneity of small cell lung cancer

Lydia Meder  1   2 , Reinhard Büttner  2   3   4 , Margarete Odenthal  2   3
Affiliations
Editorial

Notch signaling triggers the tumor heterogeneity of small cell lung cancer

Lydia Meder et al. J Thorac Dis. 2017 Dec.
No abstract available

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Scheme of lung cancer trans-differentiation. (A) SCLC is initially sensitive to chemotherapy. Upon acquired chemotherapy resistance, the relapsed tumor frequently presents large non-neuroendocrine tumor cells referring to a NSCLC phenotype; (B) NSCLCs harboring mutated EGFR may be treated by tyrosine kinase inhibitors (TKIs). Tumors that acquired resistance to TKIs frequently relapse as combined SCLCs, comprising a neuroendocrine small cell and a non-neuroendocrine non-small cell compartment; (C) SCLCs primarily originate from neuroendocrine precursors with inactivated Notch signaling, low Hes1 and Rest levels and high ASCL1 expression. RB1 and TP53 represent the most frequently mutated genes in SCLC. For NSCLCs, non-neuroendocrine precursors are the predominant cells of origin. They show activated Notch signaling with high levels of Hes1 and Rest and low ASCL1 expression. The trans-differentiation from SCLC to NSCLC phenotypes might be triggered mainly by ASCL1, whereas Rest is suggested as the master regulator in the trans-differentiation from NSCLC to SCLC. NE, neuroendocrine; non-NE, non-neuroendocrine; SCLC, small cell lung cancer; NSCLC, non-small cell lung cancer.
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References

    1. Lim JS, Ibaseta A, Fischer MM, et al. Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer. Nature 2017;545:360-4. 10.1038/nature22323 - DOI - PMC - PubMed
    1. Crabtree JS, Singleton CS, Miele L. Notch Signaling in Neuroendocrine Tumors. Front Oncol 2016;6:94. 10.3389/fonc.2016.00094 - DOI - PMC - PubMed
    1. Osada H, Tomida S, Yatabe Y, et al. Roles of achaete-scute homologue 1 in DKK1 and E-cadherin repression and neuroendocrine differentiation in lung cancer. Cancer Res 2008;68:1647-55. 10.1158/0008-5472.CAN-07-5039 - DOI - PubMed
    1. Jacobsen TL, Brennan K, Arias AM, et al. Cis-interactions between Delta and Notch modulate neurogenic signalling in Drosophila. Development 1998;125:4531-40. - PubMed
    1. Fleming RJ, Hori K, Sen A, et al. An extracellular region of Serrate is essential for ligand-induced cis-inhibition of Notch signaling. Development 2013;140:2039-49. 10.1242/dev.087916 - DOI - PMC - PubMed

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