Crizotinib inhibits migration and expression of ID1 in MET-positive lung cancer cells: implications for MET targeting in oncology

Stutz, Emanuel; Gautschi, Oliver; Fey, Martin F.; Gugger, Mathias; Tschan, Mario; Rothschild, Sacha I. (2014). Crizotinib inhibits migration and expression of ID1 in MET-positive lung cancer cells: implications for MET targeting in oncology. Future oncology, 10(2), pp. 211-217. Future Medicine Ltd. 10.2217/fon.13.179

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ABSTRACT Aims: ID1 is an important component of the MET-SRC signaling pathway, which is a regulator of cell migration and invasion. We hypothesized that the ALK/MET inhibitor crizotinib inhibits migration via MET-SRC-ID1, rather than ALK. Materials & methods: We used ALK fusion-positive and -negative lung cancer cell lines; crizotinib, PHA-665752, and saracatinib, and stable transfection with shMET. We performed western blotting for p-ALK, ALK, p-MET, MET, p-SRC, SRC and ID1, and quantitative real-time PCR for ID1. Results: Crizotinib decreased p-MET, p-SRC and ID1 levels in ALK- and or MET-positive cell lines and inhibited cell migration. Knockdown of MET was comparable with the effect of crizotinib. Conclusion: The effects of crizotinib on ID1 expression and cancer cell migration were associated with the presence of activated MET, rather than ALK fusion.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Med. Onkologie / Hämatologie (Erw.) 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Med. Onkologie / Hämatologie (Erw.) 04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology 04 Faculty of Medicine > Service Sector > Institute of Pathology
Graduate School:	Graduate School for Cellular and Biomedical Sciences (GCB)
UniBE Contributor:	Gautschi, Oliver, Fey, Martin, Gugger, Mathias, Tschan, Mario Paul, Rothschild, Sacha
Subjects:	600 Technology > 610 Medicine & health 500 Science > 570 Life sciences; biology
ISSN:	1479-6694
Publisher:	Future Medicine Ltd.
Language:	English
Submitter:	Andrea Arnold
Date Deposited:	02 Apr 2014 14:52
Last Modified:	05 Dec 2022 14:31
Publisher DOI:	10.2217/fon.13.179
PubMed ID:	24490607
URI:	https://boris.unibe.ch/id/eprint/46099