Role of STAT3 in tumor angiogenesis and radiation sensitivity / 中国肿瘤临床

ABSTRACT

Signal transducer and activator of transcription 3 (STAT3) is an important member of the STAT family of signaling pro-teins. STAT3 is widely expressed in different types of cells and tissues and is involved in many physiological and pathological process-es, including cell growth, proliferation, apoptosis, and malignant transformation. Over recent years, increased attention has been given on the role of STAT3 in tumor angiogenesis and radiation sensitivity. Studies show that on the one hand, following activation, STAT3 promotes angiogenesis by directly regulating the expression of vascular endothelial growth factor and then causes radiation resistance. On the other hand, STAT3 indirectly promotes angiogenesis by activating hypoxia-inducible factor-1α(HIF-1α), thus producing radio-therapy tolerance. Moreover, STAT3 can directly or by HIF-1αindirectly regulate CyclinD1 expression, thus rapidly promoting cell pro-gression through G1 into the S phase of the cell cycle and enhancing cell proliferation. In addition to regulating the cell cycle, CyclinD1 plays a key role in radiation sensitivity. Results suggest that STAT3 plays a role in tumor angiogenesis and radiation resistance via di-rect and indirect mechanisms. In this review, we summarize recent research advances on the role of STAT3 in regulating tumor angio-genesis and radiation sensitivity.