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 and 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:

02 Feb 2016 10:56

Publisher DOI:

10.2217/fon.13.179

PubMed ID:

24490607

URI:

https://boris.unibe.ch/id/eprint/46099

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