Poster Presentation 30th Lorne Cancer Conference 2018

The complex roles of STAT3 in Myc-driven tumourigenesis (#166)

Aleks Guanizo 1 , Jasmine Chen 1 , Samantha Jayasekara 1 , Daniel Gough 1 , Neil Watkins 2
  1. Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, VICTORIA, Australia
  2. Cancer Developmental Biology, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor critical for cellular growth, differentiation, immune function, metabolism and survival. Aberrant STAT3 activation has been observed in approximately 50% of human cancers, and has been linked to tumour progression and therapeutic resistance. One key target gene of STAT3 is Myc which is a potent transcription factor with oncogenic potential as observed in at least 40% of tumours. The STAT3-dependent induction of Myc expression in tumours has been presumed to be a key event in STAT3-driven tumour process. It would therefore, be expected that in tumours with mutations in MYC resulting in sustained expression, that STAT3 would no longer be required. However, our data shows that STAT3 signalling remains critical in maintaining tumourigenesis in cancers with forced Myc expression. However, whether STAT3 is a proto-oncogene or a tumour suppressor depends on the tumour type. We found that STAT3 is required for Myc-induced transforming capacity of mouse embryonic fibroblasts. STAT3 also drives tumourigenic potential of Myc-amplified epithelial-derived cancer cell lines, such as Hs578t breast cancer cell, and SW480 and HCT-116 colorectal cancer cell lines. Interestingly, STAT3 displays tumour inhibitory activity in cancer cells of neuroendocrine origin, including small cell lung cancer (SCLC). When translated into a MYC-driven mouse model of small cell lung cancer (a neuroendocrine tumour) we observe that STAT3 loss corresponds to a decrease in primary tumour burden but a significant increase in metastatic disease. These data highlight the complex activities of STAT3 in tumours.