Podocalyxin-like protein promotes gastric cancer progression through interacting with RUN and FYVE domain containing 1 protein.
Podocalyxin-like protein promotes gastric cancer progression through interacting with RUN and FYVE domain containing 1 protein.
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DOI：
10.1111/cas.13864
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发表时间：
2019-01
期刊：
影响因子：
5.7
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Zhi Q;Chen H;Liu F;Han Y;Wan D;Xu Z;Kuang Y;Zhou J
Podocalyxin‐like protein (PODXL), a transmembrane glycoprotein with anti‐adhesive properties, is associated with an aggressive tumor phenotype and poor prognosis of several cancers. To elucidate the biological significance of PODXL and its molecular mechanism in gastric cancer (GC), we investigated the expression of PODXL in GC samples and assessed its effects on biological behaviors and the related signaling pathways in vitro and in vivo. Moreover, the possible and closely interacted partners of PODXL were identified. Our data showed that the protein or mRNA level of PODXL was significantly upregulated in tissues or serum of GC patients compared with normal‐appearing tissues (NAT) or those of healthy volunteers. Overall survival (OS) curves showed that patients with high PODXL levels in tissues or serum had a worse 5‐year OS. In vitro, restoring PODXL expression promoted tumor progression by increasing cell proliferation, colony formation, wound healing, migration and invasion, as well as suppressing the apoptosis. Furthermore, the PI3K/AKT, NF‐κB and MAPK/ERK signaling pathways were activated. There was a significant positive correlation between PODXL and RUN and FYVE domain containing 1 (RUFY1) expression in tissues or serum. Subsequent mass spectrometry analysis, co‐immunoprecipitation assays and western blot analysis identified PODXL/RUFY1 complexes in GC cells, and silencing RUFY1 expression in GC cells significantly attenuated PODXL‐induced phenotypes and their underlying signaling pathways. Our results suggested that PODXL promoted GC progression via a RUFY1‐dependent signaling mechanism. New GC therapeutic opportunities through PODXL and targeting the PODXL/RUFY1 complex might improve cancer therapy.
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影响因子：
--
作者：
Borg D;Hedner C;Nodin B;Larsson A;Johnsson A;Eberhard J;Jirström K
通讯作者：
Jirström K
影响因子：
--
作者：
Huang TC;Renuse S;Pinto S;Kumar P;Yang Y;Chaerkady R;Godsey B;Mendell JT;Halushka MK;Civin CI;Marchionni L;Pandey A
通讯作者：
Pandey A
影响因子：
6
作者：
Hsu, Yung-Ho;Lin, Wei-Ling;Jou, Tzuu-Shuh
通讯作者：
Jou, Tzuu-Shuh
DOI：
10.1084/jem.187.12.1965
发表时间：
1998-06-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Sassetti C;Tangemann K;Singer MS;Kershaw DB;Rosen SD
通讯作者：
Rosen SD
DOI：
10.1016/j.jcmgh.2017.02.003
发表时间：
2017-05
影响因子：
7.2
作者：
Liu X;Meltzer SJ
通讯作者：
Meltzer SJ