S100P and Ezrin promote trans-endothelial migration of triple negative breast cancer cells

Kyoko Kikuchi, Keely May Mcnamara, Yasuhiro Miki, Erina Iwabuchi, Ayako Kanai, Minoru Miyashita, Takanori Ishida, Hironobu Sasano

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


Purpose: Triple negative breast cancer (TNBC) patients generally have an adverse clinical outcome because their tumors often recur and metastasize to distant sites in the first 3 years after surgery. Therefore, it has become pivotal to identify potential factors associated with metastasis. Here, we focused on the effects of S100P and Ezrin on the trans-endothelial migration (TEM) of TNBC cells, as they have both been suggested to play a role in this process in other malignancies. Methods: The expression of S100P and Ezrin was examined by immunohistochemistry in 58 primary TNBC samples. The mRNA and protein levels of S100P and Ezrin were assessed in breast cancer-derived cell lines using qRT-PCR and Western blotting, respectively. Proliferation and migration assays were performed using TNBC-derived MFM-223 and SUM-185-PE cells transfected with S100P and Ezrin siRNAs. Two different timeframes were employed for TEM assays using TNBC-derived cells and human umbilical vein endothelial-derived cells, respectively. Correlations between the status of Ezrin Thr-567 expression and various clinicopathological features were analyzed by immunohistochemistry. Results: We found that S100P and Ezrin double negative TNBC cases were significantly associated with a better disease-free survival. We also found that single and double siRNA-mediated knockdown of S100P and Ezrin in TNBC-derived cells significantly inhibited their TEM and destabilized the intercellular junctions of endothelial cells. In addition, we found that Ezrin Thr-567 immunoreactivity significantly correlated with vascular invasion in TNBC patients. Conclusions: From our data we conclude that S100P, Ezrin and Ezrin Thr-567 are involved in the trans-endothelial migration of TNBC cells and that they may serve as potential targets in TNBC patients.

Original languageEnglish
Pages (from-to)67-80
Number of pages14
JournalCellular Oncology
Issue number1
Publication statusPublished - 2019 Feb 15


  • Ezrin
  • S100P
  • Trans-endothelial migration
  • Triple negative breast carcinoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research


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