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.

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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