scholarly journals PD-L1 interacts with Frizzled 6 to activate β-catenin and form a positive feedback loop to promote cancer stem cell expansion

Oncogene ◽  
2022 ◽  
Lingchen Fu ◽  
Jia Fan ◽  
Sudipa Maity ◽  
Grant McFadden ◽  
Yixin Shi ◽  
2020 ◽  
Vol 177 (1) ◽  
pp. 71-83
Marco Clementino ◽  
Jie Xie ◽  
Ping Yang ◽  
Yunfei Li ◽  
Hsuan-Pei Lin ◽  

Abstract Chronic hexavalent chromium [Cr(VI)] exposure causes lung cancer and other types of cancer; however, the mechanism of Cr(VI) carcinogenesis remains to be clearly defined. Our recent study showed that chronic Cr(VI) exposure upregulates the proto oncogene c-Myc expression, which contributes significantly to Cr(VI)-induced cell transformation, cancer stem cell (CSC)-like property and tumorigenesis. c-Myc is a master regulator of cancer cell abnormal metabolism and accumulating evidence suggests that metabolism dysregulation plays an important role in both cancer development and progression. However, little is known about the role of metabolism dysregulation in Cr(VI) carcinogenesis. This study was performed to investigate the potential role and mechanism of metabolism dysregulation in Cr(VI) carcinogenesis. It was found that Cr(VI)-transformed cells display glycolytic shift, which depends on the upregulation of c-Myc. The glycolytic shift in Cr(VI)-transformed cells led to increased production of acetyl coenzyme A (acetyl-CoA) and elevation of histone acetylation. This, in turn, upregulated the expression of an acetyl-CoA producing key enzyme ATP citrate lyase and c-Myc, forming a positive feedback loop between the upregulation of c-Myc expression, glycolytic shift and increased histone acetylation. It was further determined that glucose depletion not only reverses the glycolytic shift in Cr(VI)-transformed cells, but also significantly reduces their growth, CSC-like property and tumorigenicity. These findings indicate that glycolytic shift plays an important role in maintaining malignant phenotypes of Cr(VI)-transformed cells, suggesting that metabolism dysregulation is critically involved in Cr(VI) carcinogenesis.

2020 ◽  
Vol 123 (6) ◽  
pp. 955-964
Kazuya Iwamoto ◽  
Hidekazu Takahashi ◽  
Daisuke Okuzaki ◽  
Hideo Osawa ◽  
Takayuki Ogino ◽  

2020 ◽  
Vol 395 (2) ◽  
pp. 112183
Rong-Zheng Ran ◽  
Jun Chen ◽  
Long-Jiu Cui ◽  
Xiao-Lu Lin ◽  
Ming-Ming Fan ◽  

2012 ◽  
Jia Ke ◽  
Fayaz A. Malik ◽  
Sean McDermott ◽  
Rachel Martin ◽  
Li Shang ◽  

Cell Cycle ◽  
2020 ◽  
Vol 19 (10) ◽  
pp. 1077-1088 ◽  
Caifeng Liu ◽  
Jun Li ◽  
Wei Wang ◽  
Xingyang Zhong ◽  
Feng Xu ◽  

2015 ◽  
Vol 149 (7) ◽  
pp. 1884-1895.e4 ◽  
Dingzhi Wang ◽  
Lingchen Fu ◽  
Haiyan Sun ◽  
Lixia Guo ◽  
Raymond N. DuBois

2020 ◽  
Vol 19 (7) ◽  
pp. 1474-1485 ◽  
Alexander Rau ◽  
Wolfgang S. Lieb ◽  
Oliver Seifert ◽  
Jonas Honer ◽  
Dennis Birnstock ◽  

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