GATA1 promotes colorectal cancer cell proliferation, migration and invasion via activating AKT signaling pathway
GATA1, a member of the GATA transcription factor family, was reported to play a role in development and progression of erythroid cells and breast cancer cells. However, the role of GATA1 in colorectal cancer (CRC) is unknown. Here, we demonstrate that GATA1 was upregulated in CRC tissues compared with normal tissues, and predicted poor clinical outcome in CRC. Biological functional analyses showed that GATA1 knockdown decreased CRC cells proliferation, migration and invasion, and regulated the process of epithelial–mesenchymal transition (EMT). Moreover, silencing of GATA1 suppressed colorectal tumor growth in nude mice. Mechanistically, GATA1 overexpression significantly increased the activity of PI3K/AKT signaling pathway in CRC cells. These data provide insight into the important role of GATA1 in CRC progression and suggest that GATA1 is a potential therapeutic target for CRC.
KeywordsColorectal cancer GATA1 Tumor progression AKT
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All applicable international, national, and institutional guidelines for the care and use of animals were followed.
Informed consent was obtained from all individual participants included in the study.
- 13.Zhang Y, Liu J, Lin J, Zhou L, Song Y, Wei B, Luo X, Chen Z, Chen Y, Xiong J, Xu X, Ding L, Ye Q (2016) The transcription factor GATA1 and the histone methyltransferase SET7 interact to promote VEGF-mediated angiogenesis and tumor growth and predict clinical outcome of breast cancer. Oncotarget 7:9859–9875Google Scholar
- 14.Li Y, Ke Q, Shao Y, Zhu G, Li Y, Geng N, Jin F, Li F (2015) GATA1 induces epithelial-mesenchymal transition in breast cancer cells through PAK5 oncogenic signaling. Oncotarget 6:4345–4356Google Scholar
- 21.Grille SJ, Bellacosa A, Upson J, Klein-Szanto AJ, Roy FV, Lee-Kwon W, Donowitz M, Tsichlis PN, Larue L (2003) The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res 63:2172–2178Google Scholar
- 26.Danielsen SA, Eide PW, Nesbakken A, Guren T, Leithe E, Lothe RA (2015) Portrait of the PI3K/AKT pathway in colorectal cancer. Biochim Biophys Acta 1855:104–121Google Scholar