Open Access
Cancers, volume 12, issue 6, pages 1674
Inhibition of FGF2-Mediated Signaling in GIST—Promising Approach for Overcoming Resistance to Imatinib
Boichuk Sergei
1, 2
,
Galembikova Aigul
2
,
Mikheeva Ekaterina
2
,
Bikinieva Firuza
2
,
Aukhadieva Aida
2
,
Dunaev Pavel
2
,
Khalikov Dinar
3
,
Petrov Semen
2, 3
,
Kurtasanov Refat
3
,
Valeeva Elena
1
,
Kireev Igor
4, 5
,
Dugina Vera
6
,
Lushnikova Anna
7
,
Novikova Maria
8
,
3
Tatarstan Cancer Center, 420029 Kazan, Russia
|
Publication type: Journal Article
Publication date: 2020-06-24
PubMed ID:
32599808
Cancer Research
Oncology
Abstract
Inhibition of KIT-signaling is a major molecular target for gastrointestinal stromal tumor (GIST) therapy, and imatinib mesylate (IM) is known as the most effective first-line treatment option for patients with advanced, unresectable, and/or metastatic GISTs. We show here for the first time that the inhibition of KIT-signaling in GISTs induces profound changes in the cellular secretome, leading to the release of multiple chemokines, including FGF-2. IM increased migration, invasion, and colony formation of IM-resistant GISTs in an FGF2-dependent manner, whereas the use of blocking anti-FGF2 antibodies or BGJ398, a selective FGFR inhibitor, abolished these effects, thus suggesting that the activation of FGF2-mediated signaling could serve as a compensatory mechanism of KIT-signaling inhibited in GISTs. Conversely, FGF-2 rescued the growth of IM-naive GISTs treated by IM and protected them from IM-induced apoptosis, consistent with the possible involvement of FGF-2 in tumor response to IM-based therapy. Indeed, increased FGF-2 levels in serum and tumor specimens were found in IM-treated mice bearing IM-resistant GIST xenografts, whereas BGJ398 used in combination with IM effectively inhibited their growth. Similarly, increased FGF-2 expression in tumor specimens from IM-treated patients revealed the activation of FGF2-signaling in GISTs in vivo. Collectively, the continuation of IM-based therapy for IM-resistant GISTs might facilitate disease progression by promoting the malignant behavior of tumors in an FGF2-dependent manner. This provides a rationale to evaluate the effectiveness of the inhibitors of FGF-signaling for IM-resistant GISTs.
Citations by journals
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1
2
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Cancers
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World Journal of Gastrointestinal Oncology
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1 publication, 10%
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1 publication, 10%
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Journal of Oncology
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1 publication, 10%
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Pharmacology and Therapeutics
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1 publication, 10%
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1 publication, 10%
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Oncology Letters
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1 publication, 10%
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Advances in molecular oncology
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1 publication, 10%
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1
2
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Citations by publishers
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1
2
3
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Multidisciplinary Digital Publishing Institute (MDPI)
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Multidisciplinary Digital Publishing Institute (MDPI)
3 publications, 30%
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Baishideng Publishing Group
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Baishideng Publishing Group
1 publication, 10%
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Springer Nature
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Springer Nature
1 publication, 10%
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Hindawi Limited
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Hindawi Limited
1 publication, 10%
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Elsevier
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Elsevier
1 publication, 10%
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Eco-Vector LLC
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Eco-Vector LLC
1 publication, 10%
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Spandidos Publications
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Spandidos Publications
1 publication, 10%
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Publishing House ABV Press
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Publishing House ABV Press
1 publication, 10%
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1
2
3
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Boichuk S. et al. Inhibition of FGF2-Mediated Signaling in GIST—Promising Approach for Overcoming Resistance to Imatinib // Cancers. 2020. Vol. 12. No. 6. p. 1674.
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Boichuk S., Galembikova A., Mikheeva E., Bikinieva F., Aukhadieva A., Dunaev P., Khalikov D., Petrov S., Kurtasanov R., Valeeva E., Kireev I., Dugina V., Lushnikova A., Novikova M., Kopnin P. Inhibition of FGF2-Mediated Signaling in GIST—Promising Approach for Overcoming Resistance to Imatinib // Cancers. 2020. Vol. 12. No. 6. p. 1674.
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TY - JOUR
DO - 10.3390/cancers12061674
UR - https://doi.org/10.3390%2Fcancers12061674
TI - Inhibition of FGF2-Mediated Signaling in GIST—Promising Approach for Overcoming Resistance to Imatinib
T2 - Cancers
AU - Mikheeva, Ekaterina
AU - Aukhadieva, Aida
AU - Khalikov, Dinar
AU - Kurtasanov, Refat
AU - Valeeva, Elena
AU - Kireev, Igor
AU - Lushnikova, Anna
AU - Petrov, Semen
AU - Novikova, Maria
AU - Dunaev, Pavel
AU - Galembikova, Aigul
AU - Dugina, Vera
AU - Boichuk, Sergei
AU - Bikinieva, Firuza
AU - Kopnin, Pavel
PY - 2020
DA - 2020/06/24 00:00:00
PB - Multidisciplinary Digital Publishing Institute (MDPI)
SP - 1674
IS - 6
VL - 12
PMID - 32599808
SN - 2072-6694
ER -
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@article{2020_Boichuk,
author = {Ekaterina Mikheeva and Aida Aukhadieva and Dinar Khalikov and Refat Kurtasanov and Elena Valeeva and Igor Kireev and Anna Lushnikova and Semen Petrov and Maria Novikova and Pavel Dunaev and Aigul Galembikova and Vera Dugina and Sergei Boichuk and Firuza Bikinieva and Pavel Kopnin},
title = {Inhibition of FGF2-Mediated Signaling in GIST—Promising Approach for Overcoming Resistance to Imatinib},
journal = {Cancers},
year = {2020},
volume = {12},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
month = {jun},
url = {https://doi.org/10.3390%2Fcancers12061674},
number = {6},
pages = {1674},
doi = {10.3390/cancers12061674}
}
Cite this
MLA
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Boichuk, Sergei, et al. “Inhibition of FGF2-Mediated Signaling in GIST—Promising Approach for Overcoming Resistance to Imatinib.” Cancers, vol. 12, no. 6, Jun. 2020, p. 1674. https://doi.org/10.3390%2Fcancers12061674.