scholarly journals Roles of Mitochondrial Serine Hydroxymethyltransferase 2 (SHMT2) in Human Carcinogenesis

2021 ◽  
Vol 12 (19) ◽  
pp. 5888-5894
Author(s):  
Yuanyuan Zeng ◽  
Jie Zhang ◽  
Mengmeng Xu ◽  
Fuxian Chen ◽  
Ruidong Zi ◽  
...  
Keyword(s):  
Serine Hydroxymethyltransferase ◽  
Human Carcinogenesis

scholarly journals Structure and reactivity of cysteine residues in mitochondrial serine hydroxymethyltransferase.

1983 ◽  
Vol 258 (21) ◽  
pp. 13155-13159 ◽  
Author(s):  
F Gavilanes ◽  
D Peterson ◽  
B Bullis ◽  
L Schirch
Keyword(s):  
Serine Hydroxymethyltransferase ◽  
Cysteine Residues

scholarly journals The loss of SHMT2 mediates 5-fluorouracil chemoresistance in colorectal cancer by upregulating autophagy

Oncogene ◽  
2021 ◽  
Author(s):  
Jian Chen ◽  
Risi Na ◽  
Chao Xiao ◽  
Xiao Wang ◽  
Yupeng Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Patient Survival ◽  
Serine Hydroxymethyltransferase ◽  
First Line ◽  
Xenograft Models ◽  
Potential Opportunity ◽  
First Line Treatment ◽  
Novel Therapeutic

Abstract5-Fluorouracil (5-FU)-based chemotherapy is the first-line treatment for colorectal cancer (CRC) but is hampered by chemoresistance. Despite its impact on patient survival, the mechanism underlying chemoresistance against 5-FU remains poorly understood. Here, we identified serine hydroxymethyltransferase-2 (SHMT2) as a critical regulator of 5-FU chemoresistance in CRC. SHMT2 inhibits autophagy by binding cytosolic p53 instead of metabolism. SHMT2 prevents cytosolic p53 degradation by inhibiting the binding of p53 and HDM2. Under 5-FU treatment, SHMT2 depletion promotes autophagy and inhibits apoptosis. Autophagy inhibitors decrease low SHMT2-induced 5-FU resistance in vitro and in vivo. Finally, the lethality of 5-FU treatment to CRC cells was enhanced by treatment with the autophagy inhibitor chloroquine in patient-derived and CRC cell xenograft models. Taken together, our findings indicate that autophagy induced by low SHMT2 levels mediates 5-FU resistance in CRC. These results reveal the SHMT2–p53 interaction as a novel therapeutic target and provide a potential opportunity to reduce chemoresistance.

Role of FGFs and FGF Receptors in Human Carcinogenesis

1991 ◽  
Vol 638 (1 The Fibroblas) ◽  
pp. 409-411 ◽  
Author(s):  
D. BIRNBAUM ◽  
O. deLAPEYRIERE,a ◽  
J. ADNANE ◽  
C. DIONNE ◽  
G. CRUMLEY ◽  
...  
Keyword(s):  
Human Carcinogenesis
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