Akt-girdin signaling in cancer-associated fibroblasts contributes to tumor progression

Yumiko Yamamura, Naoya Asai, Atsushi Enomoto, Takuya Kato, Shinji Mii, Yuji Kondo, Kaori Ushida, Kaoru Niimi, Nobuyuki Tsunoda, Masato Nagino, Shu Ichihara, Koichi Furukawa, Kengo Maeda, Toyoaki Murohara, Masahide Takahashi

Research output: Contribution to journalArticlepeer-review

102 Citations (Scopus)


PI3K-Akt signaling is critical for the development, progression, and metastasis of malignant tumors, but its role in the tumor microenvironment has been relatively little studied. Here, we report that the Akt substrate Girdin, an actin-binding protein that regulates cell migration, is expressed and activated by Akt phosphorylation in cancer-associated fibroblasts (CAF) and blood vessels within the tumor microenvironment. Lewis lung tumors grafted into mice defective in Akt-mediated Girdin phosphorylation (SA transgenic mice) exhibited a decrease in both CAF infiltration and tumor growth, compared with wild-type (WT) host control animals. Contrasting with the findings of other studies, we found that Akt-dependent phosphorylation of Girdin was not a rate-limiting step in the growth of endothelial cells. In addition, Lewis lung tumors displayed limited outgrowth when cotransplanted with CAF derived from tumor-bearing SA transgenic mice, compared with CAF derived from tumor-bearing WT mice. Collectively, our results revealed a role for Akt-mediated Girdin phosphorylation in CAF during tumor progression, highlighting the need to inhibit Akt function in both tumor cells and cells that comprise the tumor microenvironment.

Original languageEnglish
Pages (from-to)813-823
Number of pages11
JournalCancer Research
Issue number5
Publication statusPublished - 01-03-2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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