Transketolase promotes colorectal cancer metastasis through regulating AKT phosphorylation

Minle Li,Shuxi Qiao,Zhongwei Li,Hongmei Yong,Jian Xu,Sufang Chu,Junnian Zheng,Xue Zhao,Pingfu Hou,Pengfei Qu,Jin Bai

doi:10.1038/s41419-022-04575-5

Minle Li, Shuxi Qiao + Show 9 more

Open Access

https://doi.org/10.1038/s41419-022-04575-5

Copy DOI

Abstract

Transketolase (TKT) which is an important metabolic enzyme in the pentose phosphate pathway (PPP) participates in maintaining ribose 5-phosphate levels. TKT is necessary for maintaining cell growth. However, we found that in addition to this, TKT can also affect tumor progression through other ways. Our previous study indicate that TKT could promote the development of liver cancer by affecting bile acid metabolism. And in this study, we discovered that TKT expression was remarkably upregulated in colorectal cancer, abnormal high expression of TKT is associated with poor prognosis of colorectal cancer. Additionally, TKT promoted colorectal cancer cell growth and metastasis. Further study demonstrated that TKT interacted with GRP78 and promoted colorectal cancer cell glycolysis through increasing AKT phosphorylation, thereby enhancing colorectal cancer cell metastasis. Thus, TKT is expected to become an indicator for judging the prognosis of colorectal cancer, and provide a theoretical basis for drug development of new treatment targets for colorectal cancer.

Highlights

One of the characteristics of malignant tumors is enhanced aerobic glycolysis [1]
TKT was highly expressed in Colorectal cancer (CRC) and cell lines and indicated poor prognosis We tested TKT expression in 10 pairs of colorectal cancer and adjacent samples
Our results showed that TKT significantly increased aerobic glycolysis, glucose consumption, lactic acid production of CRC cells as expected (Fig. 5A–C)

Summary

Introduction

One of the characteristics of malignant tumors is enhanced aerobic glycolysis [1]. Emerging studies have revealed that glycolysis is positively correlated with the malignant progression of cancer [2, 3]. It is evident that lactate promotes tumor growth and metastasis [4,5,6]. Targeting glycolysis remains attractive for cancer therapy. Colorectal cancer (CRC) is a malignant tumor of the digestive system [7, 8], and about half of patients with CRC die due to tumor metastasis [9]. Finding a potential therapeutic target for CRC metastasis is important for clinical treatment

Methods

Results

Conclusion