title: Transketolase-like 1 expression is modulated during colorectal cancer progression and metastasis formation.
abstract: BACKGROUND
  Transketolase-like 1 (TKTL1) induces glucose degradation through anaerobic pathways, even in presence of oxygen, favoring the malignant aerobic glycolytic phenotype characteristic of tumor cells. As TKTL1 appears to be a valid biomarker for cancer prognosis, the aim of the current study was to correlate its expression with tumor stage, probability of tumor recurrence and survival, in a series of colorectal cancer patients.  METHODOLODY/PRINCIPAL FINDINGS: Tumor tissues from 63 patients diagnosed with colorectal cancer at different stages of progression were analyzed for TKTL1 by immunohistochemistry. Staining was quantified by computational image analysis, and correlations between enzyme expression, local growth, lymph-node involvement and metastasis were assessed. The highest values for TKTL1 expression were detected in the group of stage III tumors, which showed significant differences from the other groups (Kruskal-Wallis test, P = 0.000008). Deeper analyses of T, N and M classifications revealed a weak correlation between local tumor growth and enzyme expression (Mann-Whitney test, P = 0.029), a significant association of the enzyme expression with lymph-node involvement (Mann-Whitney test, P = 0.0014) and a significant decrease in TKTL1 expression associated with metastasis (Mann-Whitney test, P = 0.0004).
  
  
  CONCLUSIONS
  To our knowledge, few studies have explored the association between variations in TKTL1 expression in the primary tumor and metastasis formation. Here we report downregulation of enzyme expression when metastasis appears, and a correlation between enzyme expression and regional lymph-node involvement in colon cancer. This finding may improve our understanding of metastasis and lead to new and more efficient therapies against cancer.
authors: Departament de Bioquimica i Biologia Molecular, Facultat de Biologia, Institut de Biomedicina at Universitat de Barcelona IBUB and IDIBAPS-Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors: Santiago
authors: S
authors: Diaz-Moralli
authors: Miriam
authors: M
authors: Tarrado-Castellarnau
authors: Cristina
authors: C
authors: Alenda
authors: Antoni
authors: A
authors: Castells
authors: Marta
authors: M
authors: Cascante
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D057054:Molecular Imaging; D009367:Neoplasm Staging; D015203:Reproducibility of Results; D016019:Survival Analysis; D014174:Transketolase / Q000378:metabolism*
chemical_list: C505431:TKTL1 protein, human; D014174:Transketolase