4.7 Article

Rho GTPase-activating protein 35 suppresses gastric cancer metastasis by regulating cytoskeleton reorganization and epithelial-to-mesenchymal transition

Journal

BIOENGINEERED
Volume 13, Issue 6, Pages 14605-14615

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/21655979.2022.2092677

Keywords

ARHGAP35; metastasis; cytoskeleton; gastric cancer; Epithelial-mesenchymal transition

Funding

  1. National Natural Science Foundation of China [81773072, 82173241]
  2. Shaanxi Foundation for innovation capacity supporting program [2020-KJXX-058]
  3. Youth Project, Lingyun Program of Fourth Military Medical University [2019cyjhsyl]
  4. Fourth Military Medical University Doctoral Science Foundation [2021D04lgf]

Ask authors/readers for more resources

This study reveals the significant role of ARHGAP35 in gastric cancer, specifically in regulating cell morphology and motility through cytoskeletal reorganization and EMT, respectively. Targeting the ARHGAP35/RhoA/E-cadherin pathway could be a potential therapeutic approach for treating gastric cancer.
Cytoskeletal reorganization and epithelial-to-mesenchymal transition (EMT) are key processes and typical characteristics of metastatic cancer cells. Rho GTPase-activating protein 35 (ARHGAP35) is a GTPase-activating protein, which has a significant effect on cell motility. However, the particular function of ARHGAP35 in gastric cancer (GC) remains unknown. In the present study, the role of ARHGAP35 in GC was investigated by in vitro loss-of-function and gain-of-function experiments. Cytoskeletal reorganization in GC cells was evaluated using immunofluorescence staining and the protein expression levels of key molecules and active RhoA were detected by western blot analysis. Additionally, the clinical evaluation of proteins in human GC tissues was assessed by immunohistochemistry. The results showed that ARHGAP35, a tumor suppressor, was downregulated in GC tissues and its decreased expression was associated with the metastatic status of GC. Additionally, Transwell and wound healing assays demonstrated that ARHGAP35 knockdown promoted cell motility in vitro. However, the above effects were abrogated following ectopic ARHGAP35 expression. Furthermore, ARHGAP35 could affect cytoskeletal reorganization via directly regulating RhoA activation. In addition, ARHGAP35 upregulated E-cadherin and attenuated EMT in GC cells. Both ARHGAP35 and E-cadherin were associated with overall survival in patients with GC, while their combination allowed for an even greater capacity for distinguishing GC patients with different prognosis. Overall, the results of the current study suggested that ARHGAP35 could directly regulate cell morphology and motility via affecting cytoskeletal reorganization and EMT via targeting RhoA and E-cadherin, respectively. Targeting the ARHGAP35/RhoA/E-cadherin pathway could be a potential approach for treating GC.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available