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Published on: March 26, 2018
Ankrd1 Promotes Lamellipodia Formation and Cell Motility via Interaction with Talin-1 in Clear Cell Renal Cell
Yuki Takai1, Sei Naito1, Hiromi Ito1
1Department of Urology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan.
Abstract:
Ankyrin repeat domain 1 (Ankrd1), a transcriptional target of Yes-associated protein (YAP), is linked to cardiomyopathy. However, its role in cancer, particularly in clear cell renal cell carcinoma (ccRCC), remains vague. In this study, we examined the expression, regulation, and function of Ankrd1 in ccRCC. High Ankrd1 expression was related to poor prognosis in patients with ccRCC in The Cancer Genome Atlas cohort. Ankrd1 expression was regulated by YAP in all ccRCC cell lines examined and also by ERK5 in a subset of ccRCC cell lines. Moreover, silencing of Ankrd1 in ccRCC cell lines resulted in decreased cell motility, whereas its overexpression increased the cell motility. Ankrd1 colocalized with F-actin in lamellipodia upon phorbol ester stimulation. Ankrd1 silencing resulted in alterations in the shape of RCC cells and caused a decrease in lamellipodia formation. Ankrd1 also colocalized with talin-1 in lamellipodia. Ankrd1 depletion repressed talin-1-mediated activation of the integrin pathway. Immunohistochemical examination of surgical specimens revealed high expression of Ankrd1 in metastatic RCC tissues compared with that in primary RCC tissues from the same patients. Collectively, these findings suggest that Ankrd1 plays a critical role in the motility of ccRCC cells through lamellipodia formation.
Insights
Ankyrin repeat domain 1 (Ankrd1) promotes clear cell renal cell carcinoma (ccRCC) cell motility and lamellipodia formation. High Ankrd1 expression correlates with poor ccRCC prognosis, suggesting its role in metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Ankyrin repeat domain 1 (Ankrd1) is linked to cardiomyopathy but its role in clear cell renal cell carcinoma (ccRCC) is unclear.
- Yes-associated protein (YAP) regulates Ankrd1, which is implicated in various cellular processes.
Purpose of the Study:
- To investigate the expression, regulation, and functional role of Ankrd1 in ccRCC.
- To determine Ankrd1's impact on ccRCC cell motility and its association with patient prognosis.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) cohort for Ankrd1 expression and prognosis.
- Examination of Ankrd1 regulation by YAP and ERK5 in ccRCC cell lines.
- Functional studies involving Ankrd1 silencing and overexpression in ccRCC cells.
- Immunohistochemical analysis of Ankrd1 expression in primary and metastatic RCC tissues.
Main Results:
- High Ankrd1 expression is associated with poor prognosis in ccRCC patients.
- Ankrd1 expression is regulated by YAP and ERK5 in ccRCC.
- Ankrd1 silencing decreases ccRCC cell motility and lamellipodia formation.
- Ankrd1 overexpression enhances ccRCC cell motility.
- Ankrd1 colocalizes with F-actin and talin-1 in lamellipodia, repressing integrin pathway activation.
- Ankrd1 is highly expressed in metastatic RCC tissues compared to primary tissues.
Conclusions:
- Ankrd1 plays a critical role in ccRCC cell motility via lamellipodia formation.
- Ankrd1 is a potential prognostic biomarker and therapeutic target for ccRCC, particularly in metastatic disease.
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