Glycolytic Remodeling Enzyme PCK2 Regulates Tumor Initiation of Prostate Cancer Cells

Wednesday, September 24, 2014 — Poster Session IV
10:00 a.m. –12:00 p.m.	FAES Academic Center	NCI	CANCER-24

Authors

• J.S. Zhao
• S.X. Hou

Abstract

Tumor-initiating cells (TICs) play an important role in tumor progression and metastasis. Identification of the factors regulating TICs may open new avenues in cancer therapy. Here we show that the selected TIC-enriched prostate cancer cell clones use more glucose and produce excess secreted lactate than their TIC-low counterparts. We identified that the phosphoenolpyruvate carboxykinase isoform 2 (PCK2) is critical for the metabolic switch and TICs in prostate cancer. The TIC-enriched clones express high level of PCK2, knockdown of PCK2 results in low TICs, an increase in reactive oxygen species (ROS), and reduced p-AKT, while knockdown of PKM2 results in high TICs, a decrease of ROS, and enhanced p-AKT. In the patient database, we found that higher PCK2 expressions are associated with more aggressive tumors and worse survival in prostate cancer patients. Thus, PCK2 can be a viable therapeutic target for more aggressive prostate tumors.

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