| 000 | 03251nlm1a2200457 4500 | ||
|---|---|---|---|
| 001 | 657244 | ||
| 005 | 20231030041503.0 | ||
| 035 | _a(RuTPU)RU\TPU\network\23746 | ||
| 035 | _aRU\TPU\network\23367 | ||
| 090 | _a657244 | ||
| 100 | _a20180122a2017 k y0engy50 ba | ||
| 101 | 0 | _aeng | |
| 102 | _aGB | ||
| 135 | _adrcn ---uucaa | ||
| 181 | 0 | _ai | |
| 182 | 0 | _ab | |
| 200 | 1 |
_aTargeting group I p21-activated kinases to control malignant peripheral nerve sheath tumor growth and metastasis _fG. V. Semenova [et al.] |
|
| 203 |
_aText _celectronic |
||
| 300 | _aTitle screen | ||
| 320 | _a[References: p. 54-30 (45 tit.)] | ||
| 330 | _aMalignant peripheral nerve sheath tumors (MPNSTs) are devastating sarcomas for which no effective medical therapies are available. Over 50% of MPSNTs are associated with mutations in NF1 tumor suppressor gene, resulting in activation of Ras and its effectors, including the Raf/Mek/Erk and PI3K/Akt/mTORC1 signaling cascades, and also the WNT/β-catenin pathway. As Group I p21-activated kinases (Group I Paks, PAK1/2/3) have been shown to modulate Ras-driven oncogenesis, we asked if these enzymes might regulate signaling in MPNSTs. In this study we found a strong positive correlation between the activity of PAK1/2/3 and the stage of human MPNSTs. We determined that reducing Group I Pak activity diminished MPNST cell proliferation and motility, and that these effects were not accompanied by significant blockade of the Raf/Mek/Erk pathway, but rather by reductions in Akt and β- catenin activity. Using the small molecule PAK1/2/3 inhibitor Frax1036 and the MEK1/2 inhibitor PD0325901, we showed that the combination of these two agents synergistically inhibited MPNST cell growth in vitro and dramatically decreased local and metastatic MPNST growth in animal models. Taken together, these data provide new insights into MPNST signaling deregulation and suggest that co-targeting of PAK1/2/3 and MEK1/2 may be effective in the treatment of patients with MPNSTs. | ||
| 461 |
_tOncogene _d1987- |
||
| 463 |
_tVol. 36, iss. 38 _v[P. 5421–5431] _d2017 |
||
| 610 | 1 | _aэлектронный ресурс | |
| 610 | 1 | _aтруды учёных ТПУ | |
| 610 | 1 | _aновообразования | |
| 610 | 1 | _aопухоли | |
| 610 | 1 | _aкорреляции | |
| 610 | 1 | _aлечение | |
| 610 | 1 | _aнервные сети | |
| 701 | 1 |
_aSemenova _bG. V. _gGalina Vasiljevna |
|
| 701 | 1 |
_aStepanova _bD. S. _gDina Sergeevna |
|
| 701 | 1 |
_aDubyk _bCara _gC. W. |
|
| 701 | 1 |
_aHandorf _gE. |
|
| 701 | 1 |
_aDeev _bS. M. _cbiologist _cthe expert of Tomsk Polytechnic University, doctor of biological Sciences _gSergey Mikhaylovich _2stltpush _3(RuTPU)RU\TPU\pers\39299 |
|
| 701 | 1 |
_aLazar _bA. J. |
|
| 701 | 1 |
_aChernoff _bJ. _gJonathan |
|
| 712 | 0 | 2 |
_aНациональный исследовательский Томский политехнический университет (ТПУ) _bФизико-технический институт (ФТИ) _bЛаборатория радиационного контроля № 31 (Лаборатория РК № 31) _h6472 _2stltpush _3(RuTPU)RU\TPU\col\19161 |
| 801 | 2 |
_aRU _b63413507 _c20180122 _gRCR |
|
| 856 | 4 | _uhttps://doi.org/10.1038/onc.2017.143 | |
| 942 | _cCF | ||