Phosphorylation and changes in the distribution of nucleolin promote tumor metastasis via the PI3K/Akt pathway in colorectal carcinoma

Abstract

Edited by Zhijie ChangKeywords: Nucleolin Metastatic VEGF Distribution PI3K/Akt Colorectal carcinoma a b s t r a c t Here, we investigated the molecular mechanism underlying the changes in the distribution of nucleolin. Our study identified PI3K/Akt signaling as an essential pathway regulating the distribution of nucleolin. Furthermore, nucleolin can interact with phospho-PI3K-p55, and changes in the distribution of nucleolin were related to its phosphorylation. Subsequently, we analyzed the correlation of VEGF and nucleolin, and found that distribution of nucleolin related to metastatic potential. Finally, blocking cell surface nucleolin influences the process of epithelial-mesenchymal transitions. This indicates that nucleolin may be a novel cancer therapy target and a predictive marker for tumor migration in colorectal carcinoma.

MiR-511 inhibits growth and metastasis of human hepatocellular carcinoma cells by targeting PIK3R3

“…We also found that the reintroduction of PIK3R3 rescued cell proliferation, migration, and invasion inhibited by miR-511, whereas PIK3R3 silencing repressed these cellular functions elevated by antimiR-511. It is well known that the AKT/mTOR pathway is a classical signal transduction pathway and that activation of AKT/mTOR plays an essential role in tumor development and progression [30]. AKT/mTOR pathway was mediated by PIK3R3 [31], which is consistent with our finding that downregulation of PIK3R3 by miR-511 alleviates phosphorylation of AKT and mTOR.…”

A DDX31/Mutant–p53/EGFR Axis Promotes Multistep Progression of Muscle-Invasive Bladder Cancer

“…Therefore, to examine whether NCL, which forms a complex with DDX31 and EGFR, is phosphorylated in the cytoplasm of cancer cells, we conducted immunoprecipitation with an anti-DDX31 antibody using nuclear/cytoplasmic fractions of UM-UC-3 cells. As expected, we observed that cytoplasmic DDX31, but not nuclear DDX31, was co-immunoprecipitated with EGFR and phosphorylated NCL (T76/T84), which was reported to play a role in tumor progression (24), in cancer cells (Fig. 4D).…”

“…In addition, we confirmed the endogenous DDX31-NCL interaction in HT1197 (H365R) cells (Supplementary Fig. S5A was reported to be associated with tumor metastasis of colorectal carcinoma via its phosphorylation status (24). Therefore, to examine whether NCL, which forms a complex with DDX31 and EGFR, is phosphorylated in the cytoplasm of cancer cells, we conducted immunoprecipitation with an anti-DDX31 antibody using nuclear/cytoplasmic fractions of UM-UC-3 cells.…”

“…To clarify the biological functions of cytoplasmic DDX31 in bladder cancer cells, we focused on nucleolin (NCL), which was previously identified as a candidate interacting partner of DDX31 by analyzing 2-dimensional converted Interestingly, recent studies have indicated that NCL is a multifunctional shuttling protein present in the nucleus and cytoplasm and on the surface of some types of cells (24). Hence, we first examined the interaction of DDX31 with NCL by co-immunoprecipitation with anti-DDX31 and anti-NCL antibodies, respectively, and found that DDX31 interacts with endogenous NCL in UM-UC-3 and J82 cells ( Fig.…”

C23 protein meditates bone morphogenetic protein-2-mediated EMT via up-regulation of Erk1/2 and Akt in gastric cancer

“…Subsequently, the phosphorylated Smad complex is linked into Smad4 and then shuttled into the cell nucleus, where the complex initiates the corresponding gene transcription and protein expression [6][7][8]. At the same time, C23 protein is reported to express in the different subcellular structures of cancer cell [9][10][11], such as colorectal cancer [12] and gliomas [14]. Notably, C23 is demonstrated to influence some receptor-mediated signaling pathways [15].…”