Open AccessPodocalyxin‐like protein promotes gastric cancer progression through interacting with RUN and FYVE domain containing 1 protein
Author(s) -
Zhi Qiaoming,
Chen Huo,
Liu Fei,
Han Ye,
Wan Daiwei,
Xu Zhihua,
Kuang Yuting,
Zhou Jin
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13864
Subject(s) - podocalyxin , protein kinase b , pi3k/akt/mtor pathway , mapk/erk pathway , western blot , signal transduction , biology , downregulation and upregulation , chemistry , cancer research , microbiology and biotechnology , biochemistry , kidney , endocrinology , podocyte , gene , proteinuria
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.