NDA@SZTAKI

HIF-3α1 promotes colorectal tumor cell growth by activation of JAK-STAT3 signaling

Xue, X.

Jungles, K.

Onder, G.

Samhoun, J.

Győrffy, Balázs

Impact Journals

2016

RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok, tumorok, onkolĂłgia

Hypoxic environment is critical in colorectal cancer (CRC) development. Most studies have mainly focused on hypoxia-inducible factor (HIF)-1α and HIF-2α as the major hypoxic transcription factors in CRC development and progression. However, the role of HIF-3α in CRC is not clear. Here we found that HIF-3α protein was increased in colorectal tumors from both mouse models and human patients. Moreover, increased HIF-3α expression was correlated with decreased survival. Overexpression of a long isoform of HIF-3α, HIF-3α1, increased cell growth in two CRC cell lines. Surprisingly, overexpressed HIF-3α1 was localized to the cytosol and increased phosphorylated signal transducer and activator of transcription 3 (p-STAT3). STAT3 inhibition effectively reduced p-STAT3 levels and cell growth induced by HIF-3α1. The activation of p-STAT3 was independent of the transcriptional activity of HIF-3α1. However, the inhibition of the upstream regulator Janus kinase (JAK) abolished HIF-3α1-induced p-STAT3 and cell growth. Together, these results demonstrated that HIF-3α1 promotes CRC cell growth by activation of the JAK-STAT3 signaling pathway through non-canonical transcription-independent mechanisms.

angol

Article

PeerReviewed

info:eu-repo/semantics/article

text

http://real.mtak.hu/36027/1/7272_110308_3_PB_1_u.pdf

Xue, X. and Jungles, K. and Onder, G. and Samhoun, J. and Győrffy, Balázs (2016) HIF-3α1 promotes colorectal tumor cell growth by activation of JAK-STAT3 signaling. Oncotarget, 7 (10). pp. 11567-11579. ISSN 1949-2553

http://real.mtak.hu/36027/

http://dx.doi.org/10.18632/oncotarget.7272

MTMT:3062142; doi:10.18632/oncotarget.7272