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Updated: Apr 17, 2026
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
ACK1 promotes gastric cancer epithelial-mesenchymal transition and metastasis through AKT-POU2F1-ECD signalling
Song-Hui Xu1,2, Jin-Zhou Huang2, Man-Li Xu2
1Biomedicine Research Center and Department of Surgery, The Third Affiliated Hospital of Guangzhou Medicine University, Guangzhou, China.
Abstract:
Amplification of the activated Cdc42-associated kinase 1 (ACK1) gene is frequent in gastric cancer (GC). However, little is known about the clinical roles and molecular mechanisms of ACK1 abnormalities in GC. Here, we found that the ACK1 protein level and ACK1 phosphorylation at Tyr 284 were frequently elevated in GC and associated with poor patient survival. Ectopic ACK1 expression in GC cells induced epithelial-mesenchymal transition (EMT) and promoted migration and invasion in vitro, and metastasis in vivo; the depletion of ACK1 induced the opposite effects. We utilized SILAC quantitative proteomics to discover that the level of the cell cycle-related protein ecdysoneless homologue (ECD) was markedly altered by ACK1. Overexpression of ECD promoted EMT, migration, and invasion in GC, similar to the effects of ACK1 overexpression. Silencing of ECD completely blocked the augmentation of ACK1 overexpression-induced EMT, migration, and invasion. Mechanistically, ACK1 phosphorylated AKT at Thr 308 and Ser 473 and activated the AKT pathway to up-regulate the transcription factor POU2F1, which directly bound to the promoter region of its novel target gene ECD and thus regulated ECD expression in GC cells. Furthermore, the phosphorylation levels of AKT at Thr 308 and Ser 473 and POU2F1 and ECD levels were positively associated with ACK1 levels in clinical GC specimens. Collectively, we have demonstrated that ACK1 promotes EMT, migration, and invasion by activating AKT-POU2F1-ECD signalling in GC cells. ACK1 may be employed as a new prognostic factor and therapeutic target for GC.
Insights
Activated Cdc42-associated kinase 1 (ACK1) promotes gastric cancer (GC) progression by activating AKT-POU2F1-ECD signaling, driving epithelial-mesenchymal transition (EMT), migration, and invasion. ACK1 may serve as a prognostic factor and therapeutic target for GC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Amplification of the activated Cdc42-associated kinase 1 (ACK1) gene is common in gastric cancer (GC).
- The clinical significance and molecular mechanisms of ACK1 dysregulation in GC remain largely uncharacterized.
- ACK1 protein levels and phosphorylation at Tyr 284 are elevated in GC, correlating with poor patient outcomes.
Purpose of the Study:
- To elucidate the role of ACK1 in GC progression.
- To identify molecular mechanisms underlying ACK1-mediated effects in GC.
- To explore ACK1 as a potential prognostic marker and therapeutic target for GC.
Main Methods:
- Quantitative proteomics (SILAC) to identify ACK1-interacting proteins.
- In vitro and in vivo experiments assessing the effects of ACK1 and ecdysoneless homologue (ECD) overexpression and depletion on GC cell behavior.
- Western blotting and immunohistochemistry to analyze protein levels and phosphorylation in GC tissues.
Main Results:
- ACK1 overexpression promoted epithelial-mesenchymal transition (EMT), migration, invasion, and metastasis in GC cells, while ACK1 depletion reversed these effects.
- ACK1 altered the levels of the cell cycle-related protein ECD.
- ACK1 phosphorylated AKT, activating the AKT pathway, which upregulated POU2F1. POU2F1 directly bound to the ECD promoter, regulating ECD expression.
- Elevated AKT phosphorylation, POU2F1, and ECD levels correlated positively with ACK1 levels in clinical GC samples.
Conclusions:
- ACK1 drives GC cell migration, invasion, and EMT by activating the AKT-POU2F1-ECD signaling axis.
- ACK1 represents a potential prognostic biomarker and therapeutic target for gastric cancer.
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