Breast Cancer Molecular Subtypes Differentially Express Gluconeogenic Rate-Limiting Enzymes-Obesity as a Crucial Player.

Autores da FMUP

• 

  Fernando Carlos De Landér Schmitt

  Autor

• Dina Raquel Aguileira Leitão

  Autor

• Raquel Ângela Silva Soares Lino

  Autor

Participantes de fora da FMUP

• Luís C
• Fernandes R
• Coimbra N
• Rigor J
• Dias P
• Fernandes R

Unidades de investigação

• Biomedicina

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• Patologia

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Breast cancer is a heterogeneous entity, where different molecular subtypes (MS) exhibit distinct prognostic and therapeutic responses. A series of 62 breast cancer samples stratified by MS was obtained from the tumor biobank of IPO-Porto. The expression of glycolysis and gluconeogenesis-regulating enzymes was investigated by immunohistochemistry. Data analysis included stratification according to MS, body mass index (BMI), and BMI with MS (mBMI). We observed significant differences in pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PCK), and fructose-1,6-bisphosphatase (FBP) tumor cell expression when stratified by MS and mBMI. The expression of these enzymes was also statistically dependent on hormonal receptors and HER2 status and correlated with pathological stage and histological grade. Obesity tended to attenuate these differences, particularly in PC expression, although these were not affected by adipocyte deposition or inflammatory infiltration at the tumor microenvironment. Nonetheless, PCK and FBP expression was also modified by the presence of obesity-associated disorders like diabetes, hypertension, and dyslipidemia. Taken together, these findings identify metabolic fingerprints for breast cancer as distinct histological types, which are affected by the presence of obesity and obesity-associated conditions. Despite the biological role of the differential expression of enzymes remaining unknown, the current study highlights the need to identify the expression of gluconeogenic-regulating enzymes as a tool for personalized medicine.

Keywords

• Warburg effect; breast cancer; cancer cell metabolism; gluconeogenesis; glycolysis; molecular subtype; obesity