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Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
Published on: October 9, 2016
Caspase-3 promotes oncogene-induced malignant transformation via EndoG-dependent Src-STAT3 phosphorylation
Chenchen Zhu1, Fushun Fan2, Chuan-Yuan Li3
1Department of Biochemistry, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, China.
Abstract:
Accumulating evidence suggests that caspase-3 plays critical roles beyond apoptosis, serving pro-survival functions in malignant transformation and tumorigenesis. However, the mechanism of non-apoptotic action of caspase-3 in oncogenic transformation remains unclear. In the present study, we show that caspase-3 is consistently activated in malignant transformation induced by exogenous expression of oncogenic cocktail (c-Myc, p53DD, Oct-4, and H-Ras) in vitro as well as in the mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) mouse model of breast cancer. Genetic ablation of caspase-3 significantly attenuated oncogene-induced transformation of mammalian cells and delayed breast cancer progression in MMTV-PyMT transgenic mice. Mechanistically, active caspase-3 triggers the translocation of endonuclease G (EndoG) from mitochondria, which migrates to the nucleus, thereby induces phosphorylation of Src-STAT3 signaling pathway to facilitate oncogenic transformation. Taken together, our data suggest that caspase-3 plays pivotal role in facilitating rather than suppressing oncogene-induced malignant transformation of mammalian cells.
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