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Title: Role of fascin-1 in carcinoma progression : translation of basic biological research to clinical epidemiology
Author: Tan, Vanessa
ISNI:       0000 0004 5916 3285
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2014
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Fascin-1 is an actin -bundling protein with important roles in cell migration. Fascin-1 is low or absent in most normal adult epithelia, yet its expression in carcinoma from many tissues correlates clinically with aggressive disease and reduced patient survival. This research aimed to systematically review and meta-analyse immunohistochemical studies of fascin-1 in relation to carcinoma progression and mortality; to investigate the potential role of FSCN1 mRNA as a prognostic biomarker for prostate carcinoma progression; and to investigate the mechanisms regulating FSCN1 transcription in prostate carcinoma cells. A combination of epidemiological (a systematic review and a cohort study) and cell biological methods were applied. The systematic review showed that fascin -1 was associated with an increased mortality risk in breast, colorectal and oesophageal carcinoma, and with metastasis in colorectal and gastric carcinoma. In the cohort study, FSCN1 mRNA was found to be measurable in plasma, serum and urine. There was preliminary evidence that urinary FSCN1 mRNA was positively associated with subsequent all-cause mortality. Using cell biological approaches, cAMP response element binding protein (CREB) , and Aryl hydrocarbon receptor (AhR) were shown to have roles in regulating FSCN1 transcriptional activity in prostate carcinoma cells. CREB was identified to regulate a suite of transcripts, many of which encode proteins that function in cell cycle progression and cell migration and thus could be relevant to prostate cancer progression. In conclusion, fascin -1 may have potential as a novel prognostic biomarker for early identification of aggressive tumours. In particular, urinary FSCN1 mRNA may be a potential prognostic biomarker for aggressive prostate cancer. However, FSCN1 mRNA was also expressed in the serum and urine of men not diagnosed with prostate cancer, indicating that the source of FSCN1 mRNA in these biological fluids needs further investigation. FSCN1 transcriptional activity in prostate carcinoma cells depends on CREB and AhR, which could be possible therapeutic targets.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available