Article
Oncology
Angela Tramonti, Elisabet Cuyas, Jose Encinar, Matthias Pietzke, Alessio Paone, Sara Verdura, Aina Arbusa, Begona Martin-Castillo, Giorgio Giardina, Jorge Joven, Alexei Vazquez, Roberto Contestabile, Francesca Cutruzzola, Javier Menendez
Summary: Metformin functions as a novel non-catalytic inhibitor of SHMT2 by disrupting the PLP-dependent oligomerization process, which could lead to the development of novel SHMT2 inhibitors.
Article
Biochemistry & Molecular Biology
Jian Chen, Risi Na, Chao Xiao, Xiao Wang, Yupeng Wang, Dongwang Yan, Guohe Song, Xueni Liu, Jiayi Chen, Huijun Lu, Chunyan Chen, Huamei Tang, Guohong Zhuang, Guangjian Fan, Zhihai Peng
Summary: This study identified SHMT2 as a critical regulator of 5-FU chemoresistance in colorectal cancer (CRC), with SHMT2 inhibiting autophagy and promoting apoptosis under 5-FU treatment. Autophagy inhibitors could reduce 5-FU resistance induced by low SHMT2 levels. Targeting the SHMT2-p53 interaction may present a novel therapeutic strategy to overcome chemoresistance in CRC.
Article
Oncology
Shuang-Yan Xie, Ding -Bo Shi, Yi Ouyang, Fei Lin, Xiao-Yu Chen, Tong -Chao Jiang, Wen Xia, Ling Guo, Huan-Xin Lin
Summary: SHMT2, highly expressed in breast cancer cells, influences breast cancer cell proliferation by regulating MAPK and VEGF signaling pathways.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Oncology
Shuang-Yan Xie, Ding-Bo Shi, Yi Ouyang, Fei Lin, Xiao-Yu Chen, Tong-Chao Jiang, Wen Xia, Ling Guo, Huan-Xin Lin
Summary: Cancer cells modulate metabolic activities in order to adapt to their growth and proliferation. This study investigates the role of the enzyme SHMT2 in breast cancer and its potential as a therapeutic target. The researchers found that SHMT2 was highly expressed in breast cancer cells and tissues, and patients with high SHMT2 expression had worse prognosis. In vitro experiments showed that manipulating SHMT2 affected breast cancer cell proliferation. RNA-seq analysis revealed that SHMT2 over-expression influenced multiple signaling pathways and biological processes. Further investigation confirmed that SHMT2 promotes breast cancer growth through the MAPK and VEGF signaling pathways.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
T. Pongnopparat, G. Tingley, Y. Gao, J. T. Brosnan, M. E. Brosnan, S. L. Christian
Summary: The oncogenic RasV12 significantly increases formate overflow, potentially providing a way for tumor cells to produce one-carbon units required for enhanced proliferation.
Article
Hematology
Anne C. Wilke, Carmen Doebele, Alena Zindel, Kwang Seok Lee, Sara A. Rieke, Michele Ceribelli, Federico Comoglio, James D. Phelan, James Q. Wang, Yana Pikman, Dominique Jahn, Bjoern Haeupl, Constanze Schneider, Sebastian Scheich, Frances A. Tosto, Hanibal Bohnenberger, Philipp Stauder, Frank Schnuetgen, Mikolaj Slabicki, Zana A. Coulibaly, Sebastian Wolf, Kamil Bojarczuk, Bjoern Chapuy, Christian H. Brandts, Philipp Stroebel, Caroline A. Lewis, Michael Engelke, Xincheng Xu, Hahn Kim, Thanh Hung Dang, Roland Schmitz, Daniel J. Hodson, Kimberly Stegmaier, Henning Urlaub, Hubert Serve, Clemens A. Schmitt, Fernando Kreuz, Gero Knittel, Joshua D. Rabinowitz, Hans Christian Reinhardt, Matthew G. Vander Heiden, Craig Thomas, Louis M. Staudt, Thorsten Zenz, Thomas Oellerich
Summary: This study identified vulnerabilities in Burkitt lymphoma (BL) through genome-scale CRISPR-Cas9 screens and validated serine hydroxymethyltransferase 2 (SHMT2) as a potential drug target. Mechanistically, SHMT2 inhibition disrupted the oncogenic transcription factor TCF3 and collapsed tonic BCR signaling, providing new perspectives for innovative therapies.
Editorial Material
Cell Biology
Mickie Bhatia, Amro Elrafie
Summary: In this study, Liu et al. show that Prmt7 can regulate the onset and progression of leukemia by inhibiting the self-renewal capacity of leukemic stem cells (LSCs) in a mouse model of chronic myeloid leukemia (CML).
Article
Biotechnology & Applied Microbiology
Yun Zhang, Zhe Liu, Xueliang Wang, Hui Jian, Haihan Xiao, Tingyi Wen
Summary: Mitochondrial serine hydroxymethyltransferase (SHMT2) supports the proliferation of bladder cancer cells by maintaining redox homeostasis and its deficiency triggers cell apoptosis through ROS-dependent, mitochondrial-mediated pathways.
CANCER GENE THERAPY
(2022)
Article
Gastroenterology & Hepatology
Ximao Cui, Yanfen Cui, Tao Du, Xiaohua Jiang, Chun Song, Shun Zhang, Chiye Ma, Yun Liu, Qing Ni, Yuzhe Gao, Guanghui Wang
Summary: The overexpression of SHMT2 in human colorectal cancer is associated with tumor progression and prognosis. Inhibition of SHMT2 can suppress colorectal cancer cell proliferation and induce cell cycle arrest by regulating UHRF1 expression.
CANADIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Review
Endocrinology & Metabolism
Shauni L. Geeraerts, Elien Heylen, Kim De Keersmaecker, Kim R. Kampen
Summary: Cancer cells reprogram their metabolism to hyperactivate serine and glycine synthesis, relying on de novo production and genetic alterations to enhance their survival and proliferation. Serine and glycine synthesis play a crucial role in cancer progression, contributing to macromolecule synthesis, oxidative stress neutralization, and regulation of biological processes like methylation.
Article
Oncology
Weiyu Kong, Zhongyuan Wang, Nuoran Chen, Yiwen Mei, Yang Li, Yulin Yue
Summary: Recent research has shown that serine metabolism plays a crucial role in papillary renal cell carcinoma (pRCC), affecting clinical outcomes and immune infiltration. Higher expression of the SHMT2 gene and increased serine metabolism are associated with poorer prognoses in pRCC.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Erica Pranzini, Elisa Pardella, Livio Muccillo, Angela Leo, Ilaria Nesi, Alice Santi, Matteo Parri, Tong Zhang, Alejandro Huerta Uribe, Tiziano Lottini, Lina Sabatino, Anna Caselli, Annarosa Arcangeli, Giovanni Raugei, Vittorio Colantuoni, Paolo Cirri, Oliver D. K. Maddocks, Paola Chiarugi, Paolo Paoli, Maria Letizia Taddei
Summary: The study reveals that alterations in serine metabolism affect the sensitivity of colorectal cancer cells to 5-FU. Resistant cells become dependent on serine by increasing its synthesis or uptake. Mitochondrial compartmentalization of one-carbon metabolism supports purine biosynthesis and DNA damage response in resistant cells.
Review
Oncology
Yuanyuan Zeng, Jie Zhang, Mengmeng Xu, Fuxian Chen, Ruidong Zi, Jicheng Yue, Yanan Zhang, Nannan Chen, Y. Eugene Chin
Summary: Cellular metabolic reprogramming has been recognized as a hallmark of human cancer, with SHMT2 playing a crucial role in supporting tumor growth in various human malignancies. Elevated expression of SHMT2 is associated with poor prognosis, highlighting its potential as a prognostic marker and target for anticancer therapies.
Article
Multidisciplinary Sciences
Kui Wang, Li Luo, Shuyue Fu, Mao Wang, Zihao Wang, Lixia Dong, Xingyun Wu, Lunzhi Dai, Yong Peng, Guobo Shen, Hai-Ning Chen, Edouard Collins Nice, Xiawei Wei, Canhua Huang
Summary: Using integrative metabolomics and transcriptomics analyses, the study reveals that hepatocellular carcinoma (HCC) tissues have increased serine levels but decreased expression of phosphoglycerate dehydrogenase (PHGDH), a key enzyme in serine biosynthesis. The increased serine levels are obtained through enhanced PHGDH catalytic activity mediated by protein arginine methyltransferase 1 (PRMT1)-mediated methylation of PHGDH at arginine 236. Furthermore, PRMT1-mediated PHGDH methylation correlates with poor prognosis for HCC patients and blocking PHGDH methylation inhibits serine synthesis and restrains HCC growth.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Won Dong Lee, Anna Chiara Pirona, Boris Sarvin, Alon Stern, Keren Nevo-Dinur, Elazar Besser, Nikita Sarvin, Shoval Lagziel, Dzmitry Mukha, Shachar Raz, Elina Aizenshtein, Tomer Shlomi
Summary: The study showed that under physiological folate levels in the cell environment, cytosolic serine-hydroxymethyltransferase (SHMT1) is the main source of 1C units in various cancers, while mitochondrial 1C flux is excessively suppressed. Tumor-specific reliance on cytosolic 1C flux is associated with poor capacity to retain intracellular folates, determined by the expression of SLC19A1.