TY  - JOUR
A1  - Tao, Ting
A1  - Su, Qiongli
A1  - Xu, Simeng
A1  - Deng, Jun
A1  - Zhou, Sichun
A1  - Zhuang, Yu
A1  - Huang, Yanjun
A1  - He, Caimei
A1  - He, Shanping
A1  - Peng, Mei
A1  - Hocher, Berthold
A1  - Yang, Xiaoping
T1  - Down-regulation of PKM2 decreases FASN expression in bladder cancer cells through AKT/mTOR/SREBP-1c axis
JF  - Journal of cellular physiology
N2  - Fatty acid synthase (FASN) catalyzing the terminal steps in the de novo biogenesis of fatty acids is correlated with low survival and high disease recurrence in patients with bladder cancer. Pyruvate kinase M2 (PKM2) regulates the final step of glycolysis levels and provides a growth advantage to tumors. However, it is unclear whether the change of PKM2 has an effect on FASN and what is the mechanisms underlying. Here we describe a novel function of PKM2 in control of lipid metabolism by mediating transcriptional activation of FASN, showing the reduced expression of sterol regulatory element binding protein 1c (SREBP-1c). We first discovered that PKM2 physically interacts with the SREBP-1c using biochemical approaches, and downregulation of PKM2 reduced the expression of SREBP-1c by inactivating the AKT/mTOR signaling pathway, which in turn directly suppressed the transcription of major lipogenic genes FASN to reduce tumor growths. Furthermore, either PKM2 inhibitor-Shikonin or FASN inhibitor-TVB-3166 alone induced a strong antiproliferative and anticolony forming effect in bladder cancer cell line. The combination of both inhibitors exhibits a super synergistic effect on blocking the bladder cancer cells growth. It provides a new target and scientific basis for the treatment of bladder cancer.
KW  - bladder cancer cells
KW  - FASN
KW  - p-AKT
KW  - PKM2
KW  - p-mTOR
KW  - SREBP-1c
Y1  - 2018
U6  - https://doi.org/10.1002/jcp.27129
SN  - 0021-9541
SN  - 1097-4652
VL  - 234
IS  - 3
SP  - 3088
EP  - 3104
PB  - Wiley
CY  - Hoboken
ER  -