TY  - JOUR
AU  - Dragoj, Miodrag
AU  - Jovanović Stojanov, Sofija
AU  - Pešić, Milica
AU  - Stanković, Tijana
AU  - Banković, Jasna
AU  - Sereti, Evangelia
AU  - Dimas, Konstantinos
PY  - 2017
UR  - http://link.springer.com/10.1007/s10637-017-0494-4
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2822
AB  - Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer. At the time of diagnosis, a large percentage of NSCLC patients have already developed metastasis, responsible for extremely high mortality rates. CXCR4 receptor and focal adhesion kinase (FAK) are known to regulate such invasive cancer behavior. Their expression is downregulated by p53 and PTEN tumor suppressors which are commonly co-inactivated in NSCLC patients and contribute to metastasis. Therefore, targeting CXCR4 or FAK seems to be a promising strategy in suppressing metastatic spread of p53/PTEN deficient NSCLCs. In this study, we first examined the invasive characteristics of NSCLC cells with suppressed p53 and PTEN activity using wound healing, gelatin degradation and invasion assays. Further, changes in the expression of CXCR4 and FAK were evaluated by RT-qPCR and Western Blot analysis. Finally, we tested the ability of CXCR4 and FAK inhibitors (WZ811 and PF-573228, respectively) to suppress the migratory and invasive potential of p53/PTEN deficient NSCLC cells, in vitro and in vivo using metastatic models of human NSCLC. Our results showed that cells with mutually inactive p53 and PTEN have significantly increased invasive potential associated with hyperactivation of CXCR4 and FAK signaling pathways. Treatments with WZ811 and PF-573228 inhibitors significantly reduced migratory and invasive capacity in vitro and showed a trend of improved survival in vivo. Accordingly, we demonstrated that p53/PTEN deficient NSCLCs have extremely invasive phenotype and provided a rationale for the use of CXCR4 or FAK inhibitors for the suppression of NSCLC dissemination.
T2  - Investigational New Drugs
T1  - Anti-invasive effects of CXCR4 and FAK inhibitors in non-small cell lung carcinomas with mutually inactivated p53 and PTEN tumor suppressors
IS  - 6
VL  - 35
DO  - 10.1007/s10637-017-0494-4
SP  - 718
EP  - 732
ER  - 

@article{
author = "Dragoj, Miodrag and Jovanović Stojanov, Sofija and Pešić, Milica and Stanković, Tijana and Banković, Jasna and Sereti, Evangelia and Dimas, Konstantinos",
year = "2017",
abstract = "Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer. At the time of diagnosis, a large percentage of NSCLC patients have already developed metastasis, responsible for extremely high mortality rates. CXCR4 receptor and focal adhesion kinase (FAK) are known to regulate such invasive cancer behavior. Their expression is downregulated by p53 and PTEN tumor suppressors which are commonly co-inactivated in NSCLC patients and contribute to metastasis. Therefore, targeting CXCR4 or FAK seems to be a promising strategy in suppressing metastatic spread of p53/PTEN deficient NSCLCs. In this study, we first examined the invasive characteristics of NSCLC cells with suppressed p53 and PTEN activity using wound healing, gelatin degradation and invasion assays. Further, changes in the expression of CXCR4 and FAK were evaluated by RT-qPCR and Western Blot analysis. Finally, we tested the ability of CXCR4 and FAK inhibitors (WZ811 and PF-573228, respectively) to suppress the migratory and invasive potential of p53/PTEN deficient NSCLC cells, in vitro and in vivo using metastatic models of human NSCLC. Our results showed that cells with mutually inactive p53 and PTEN have significantly increased invasive potential associated with hyperactivation of CXCR4 and FAK signaling pathways. Treatments with WZ811 and PF-573228 inhibitors significantly reduced migratory and invasive capacity in vitro and showed a trend of improved survival in vivo. Accordingly, we demonstrated that p53/PTEN deficient NSCLCs have extremely invasive phenotype and provided a rationale for the use of CXCR4 or FAK inhibitors for the suppression of NSCLC dissemination.",
journal = "Investigational New Drugs",
title = "Anti-invasive effects of CXCR4 and FAK inhibitors in non-small cell lung carcinomas with mutually inactivated p53 and PTEN tumor suppressors",
number = "6",
volume = "35",
doi = "10.1007/s10637-017-0494-4",
pages = "718-732"
}

Dragoj, M., Jovanović Stojanov, S., Pešić, M., Stanković, T., Banković, J., Sereti, E.,& Dimas, K.. (2017). Anti-invasive effects of CXCR4 and FAK inhibitors in non-small cell lung carcinomas with mutually inactivated p53 and PTEN tumor suppressors. in Investigational New Drugs, 35(6), 718-732.
https://doi.org/10.1007/s10637-017-0494-4

Dragoj M, Jovanović Stojanov S, Pešić M, Stanković T, Banković J, Sereti E, Dimas K. Anti-invasive effects of CXCR4 and FAK inhibitors in non-small cell lung carcinomas with mutually inactivated p53 and PTEN tumor suppressors. in Investigational New Drugs. 2017;35(6):718-732.
doi:10.1007/s10637-017-0494-4 .

Dragoj, Miodrag, Jovanović Stojanov, Sofija, Pešić, Milica, Stanković, Tijana, Banković, Jasna, Sereti, Evangelia, Dimas, Konstantinos, "Anti-invasive effects of CXCR4 and FAK inhibitors in non-small cell lung carcinomas with mutually inactivated p53 and PTEN tumor suppressors" in Investigational New Drugs, 35, no. 6 (2017):718-732,
https://doi.org/10.1007/s10637-017-0494-4 . .