Phosphofructokinase‐P Modulates P44/42 MAPK Levels in HeLa Cells

ABSTRACT It is known that interfering with glycolysis leads to profound modification of cancer cell proliferation. However, energy production is not the major reason for this correlation. Here, using HeLa cells as a model for cancer, we demonstrate that phosphofructokinase‐P (PFK‐P), which is overexpressed in diverse types of cancer including HeLa cells, modulates expression of P44/42 mitogen‐activated protein kinase (MAPK). Silencing of PFK‐P did not alter HeLa cell viability or energy production, including the glycolytic rate. On the other hand, silencing of PFK‐P induced the downregulation of p44/42 MAPK, augmenting the sensitivity of HeLa cells to different drugs. Conversely, overexpression of PFK‐P promotes the upregulation of p44/42 MAPK, making the cells more resistant to the drugs. These results indicate that overexpression of PFK‐P by cancer cells is related to activation of survival pathways via upregulation of MAPK and suggest PFK‐P as a promising target for cancer therapy. J. Cell. Biochem. 118: 1216–1226, 2017. © 2016 Wiley Periodicals, Inc. PFK‐P levels modulate the expression of ERK1 and ERK2. PFK‐P levels interfere to cell responsiveness to drugs.