Cancer research (Chicago, Ill.), 2015-03, Vol.75 (5), p.813-823
2015
Details
- Autor(en) / Beteiligte
- Titel
- Akt-Girdin signaling in cancer-associated fibroblasts contributes to tumor progression
- Ist Teil von
- Cancer research (Chicago, Ill.), 2015-03, Vol.75 (5), p.813-823
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2015
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0008-5472eISSN: 1538-7445DOI: 10.1158/0008-5472.CAN-14-1317Titel-ID: cdi_proquest_miscellaneous_1660659606
- Format
- –
- Schlagworte
- Animals, Breast Neoplasms - enzymology, Breast Neoplasms - metabolism, Breast Neoplasms - pathology, Carcinoma, Ductal, Breast - enzymology, Carcinoma, Ductal, Breast - metabolism, Carcinoma, Ductal, Breast - pathology, Carcinoma, Lewis Lung - enzymology, Carcinoma, Lewis Lung - metabolism, Carcinoma, Lewis Lung - pathology, Cell Growth Processes - physiology, Cell Movement - physiology, Cell Proliferation - physiology, Disease Progression, Female, Fibroblasts - metabolism, Fibroblasts - pathology, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microfilament Proteins - metabolism, Phosphatidylinositol 3-Kinases - metabolism, Phosphorylation, Proto-Oncogene Proteins c-akt - metabolism, Signal Transduction, Vesicular Transport Proteins - metabolism