Knockdown of PKM2 and GLS1 expression can significantly reverse oxaliplatin-resistance in colorectal cancer cells
Open accessAbstract
// Wei-Qun Lu 1 , Ying-Ying Hu 1 , Xiao-Ping Lin 1 and Wei Fan 1 1 Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China Correspondence to: Wei Fan, email: jimfanwei@163.com , fanwei@sysucc.org.cn Keywords: colorectal cancer, pyruvate kinase M2 type (PKM2), kidney-type glutaminase (GLS1), knockdown, expression Received: February 07, 2017 Accepted: April 11, 2017 Published: April 24, 2017 ABSTRACT Clinical treatment for colorectal cancer (CRC) thus far encounters a huge challenge due to oxaliplatin-resistance. As crucial rate-limiting enzymes in aerobic glycolysis and glutaminolysis, pyruvate kinase M2 type (PKM2) and kidney-type glutaminase (GLS1) are proposed to carry important implications in colorectal carcinogenesis and drug-resistance. This study aimed to explore the possible association of oxaliplatin-resistance with aerobic glycolysis/glutaminolysis indexed by PKM2/GLS1 expression. PKM2 and GLS1 expression was quantified by polymerase chain reaction (PCR) and Western blot techniques in CRC cell lines. The abilities of cell formation, kinetics, migration, invasion, survival and apoptosis, as well as permeability glycoprotein (Pgp) expression were inspected before and after knocking-down PKM2/GLS1 expression. In addition, the influence of knocking-down PKM2/GLS1 expression was evaluated in vivo . Differentiated PKM2 and GLS1 expression in both THC8307 and THC8307/Oxa cell lines was identified. In the THC8307 cell line, PKM2 and GLS1 can accelerate malignant behaviors, increase oxaliplatin-resistance, upregulate Pgp expression, and inhibit cell apoptosis. Contrastingly in the THC8307/Oxa cell line, knockdown of PKM2/GLS1 expression can restrain malignant behaviors, reestablish oxaliplatin-sensitivity, downregulate Pgp expression, and induce cell apoptosis. In xenograft, knockdown of PKM2/GLS1 expression can significantly inhibit tumor growth, reduce Pgp expression, and increase tumor apoptosis. Taken together, the present findings enriched our knowledge by demonstrating a significant association of PKM2 and GLS1 with oxaliplatin-resistance in CRC. We further propose that knockdown of PKM2/GLS1 expression may constitute a novel therapeutic strategy toward effective treatment for CRC.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Genetic knockdown of GLS1 in oxaliplatin-resistant colorectal cancer inhibits cell formation, wound healing, migration, and invasion, and significantly increases apoptosis in vitro.
“In a study of oxaliplatin-resistant CRC, siRNA targeting GLS1 inhibited cell formation ability, wound healing ability, cell migration ability, and cell invasion ability and significantly increased apoptosis in vitro [27].”
From Combined blockade of EGFR and glutamine metabolism in preclinical models of colorectal cancer (2020) · cites this paper as [27]
The Results (Figure 5, Malignant behaviors of CRC cell lines) report lower cell-formation, migration, and invasion measures for GLS1-siRNA-treated oxaliplatin-resistant cells, and the Annexin V/PI assay (Figure 7) reports increased apoptosis. The paper specifically attributes the reported inhibition of wound healing to combined PKM2 and GLS1 knockdown, not GLS1 knockdown alone. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Cancer statistics in China, 2015
Chen, W., Zheng, R., Baade, P. D., Zhang, S., Zeng, H., Bray, F., Jemal, A., Yu, X. Q., & He, J. (2016) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21338 · Cited by 17,038 · see citing works
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197 · see citing works
Siegel, R. L., Miller, K. D., & Jemal, A. (2016) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21332 · Cited by 16,003 · see citing works
Goldberg, R. M., Sargent, D. J., Morton, R. F., Fuchs, C. S., Ramanathan, R. K., Williamson, S. K., Findlay, B., Pitot, H. C., & Alberts, S. R. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2004.09.046 · Cited by 2,251 · see citing works
Glutamine addiction: a new therapeutic target in cancer
Wise, D. R., & Thompson, C. B. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.05.003 · Cited by 1,770 · see citing works
Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer
Gross, M. I., Demo, S. D., Dennison, J. B., Chen, L., Chernov-Rogan, T., Goyal, B., Janes, J. R., Laidig, G. J., Lewis, E. R., Li, J., et al. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0870 · Cited by 1,068 · see citing works
Targeting metabolic transformation for cancer therapy
Tennant, D. A., Durán, R. V., & Gottlieb, E. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2817 · Cited by 1,057 · see citing works
Intracellular ATP Levels Are a Pivotal Determinant of Chemoresistance in Colon Cancer Cells
Zhou, Y., Tozzi, F., Chen, J., Fan, F., Xia, L., Wang, J., Gao, G., Zhang, A., Xia, X., Brasher, H., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-1674 · Cited by 374 · see citing works
Tumor-Related Molecular Mechanisms of Oxaliplatin Resistance
Martinez‐Balibrea, E., Martínez‐Cardús, A., Ginés, A., de Porras, V. R., Moutinho, C., Layos, L., Manzano, J. L., Bugés, C., Bystrup, S., Esteller, M., et al. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0636 · Cited by 332 · see citing works
Tamada, M., Nagano, O., Tateyama, S., Ohmura, M., Yae, T., Ishimoto, T., Sugihara, E., Onishi, N., Yamamoto, T., Yanagawa, H., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-3024 · Cited by 275 · see citing works
Molecular mechanisms of action and prediction of response to oxaliplatin in colorectal cancer cells
Arango, D., Wilson, A. J., Shi, Q., Corner, G. A., Aranes, M., Nicholas, C., LESSER, M. L., Mariadason, J. M., & Augenlicht, L. H. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6602215 · Cited by 273 · see citing works
van den Heuvel, A. P. J., Jing, J., Wooster, R. F., & Bachman, K. E. (2012) · Cancer Biology & Therapy · doi:10.4161/cbt.21348 · Cited by 209 · see citing works
Ge, Y., Yan, X., Jin, Y., Yang, X., Xiang, Y., Zhou, L., Han, S., Yuan, Q., & Yang, M. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005726 · Cited by 179 · see citing works
Bolzoni, M., Chiu, M., Accardi, F., Vescovini, R., Airoldi, I., Storti, P., Todoerti, K., Agnelli, L., Missale, G., Andreoli, R., et al. (2016) · Blood · doi:10.1182/blood-2016-01-690743 · Cited by 177 · see citing works
Bianchi, G., Martella, R., Ravera, S., Marini, C., Capitanio, S., Orengo, A., Emionite, L., Lavarello, C., Amaro, A., Petretto, A., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3688 · Cited by 173 · see citing works
Chemoresistance in solid tumours
Wilson, T. R., Longley, D. B., & Johnston, P. G. (2006) · Annals of Oncology · doi:10.1093/annonc/mdl280 · Cited by 171 · see citing works
Silencing of pkm2 increases the efficacy of docetaxel in human lung cancer xenografts in mice
Shi, H., Li, D., Zhang, J., Wang, Y., Li, Y., Zhang, H., Wang, X., Mu, B., Wang, W., Ma, Y., et al. (2010) · Cancer Science · doi:10.1111/j.1349-7006.2010.01562.x · Cited by 113 · see citing works
A novel human Fab antibody for Trop2 inhibits breast cancer growth in vitro and in vivo
Lin, H., Zhang, H., Wang, J., Lu, M., Zheng, F., Wang, C., Tang, X., Xu, N., Chen, R., Zhang, D., et al. (2013) · International Journal of Cancer · doi:10.1002/ijc.28451 · Cited by 90 · see citing works
Tumor metabolism, cancer cell transporters, and microenvironmental resistance
Alfarouk, K. O. (2016) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.3109/14756366.2016.1140753 · Cited by 88 · see citing works
Follow the ATP: Tumor Energy Production: A Perspective
Oronsky, B. T., Oronsky, N. C., Fanger, G. R., Parker, C. T., Caroen, S. Z., Lybeck, M., & Scicinski, J. J. (2014) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520614666140804224637 · Cited by 81 · see citing works
Zhou, C., Guo, H., Willson, A. K., Yuan, L., Jones, H. M., Gehrig, P. A., Sheng, X., Zhang, L., Clark, L. H., & Bae-Jump, V. L. (2020) · PubMed Central · doi:10.17615/2xfe-5p09 · Cited by 72 · see citing works
Zhu, H., Wu, J., Zhang, W., Luo, H., Shen, Z., Cheng, H., & Zhu, X. (2016) · Scientific Reports · doi:10.1038/srep30788 · Cited by 67 · see citing works
Martinez‐Balibrea, E., Plasencia, C., Ginés, A., Martínez‐Cardús, A., Musulén, E., Aguilera, R., Manzano, J. L., Neamati, N., & Abad, A. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0882 · Cited by 64 · see citing works
Pyruvate kinase M2 (PKM2) expression correlates with prognosis in solid cancers: a meta-analysis
Zhu, H., Luo, H., Zhu, X., Hu, X., Zheng, L., & Zhu, X. (2016) · Oncotarget · doi:10.18632/oncotarget.13703 · Cited by 63 · see citing works
Reid, M. A., Lowman, X. H., Pan, M., Tran, T. Q., Warmoes, M. O., Gabra, M. B. I., Yang, Y., Locasale, J. W., & Kong, M. (2016) · Genes & Development · doi:10.1101/gad.287235.116 · Cited by 62 · see citing works
Kap, E. J., Seibold, P., Scherer, D., Habermann, N., Balavarca, Y., Jansen, L., Zucknick, M., Becker, N., Hoffmeister, M., Ulrich, A. B., et al. (2016) · International Journal of Cancer · doi:10.1002/ijc.30026 · Cited by 57 · see citing works
High expression of MAGE-A9 correlates with unfavorable survival in hepatocellular carcinoma
Gu, X., Fu, M., Ge, Z., Zhan, F., Ding, Y., Ni, H., Zhang, W., Zhu, Y., Tang, X., Xiong, L., et al. (2014) · Scientific Reports · doi:10.1038/srep06625 · Cited by 51 · see citing works
Overman, M. J., Morris, V. K., Moinova, H., Manyam, G. C., Ensor, J., Lee, M. S., Eng, C., Kee, B. K., Fogelman, D. R., Shroff, R. T., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.11317 · Cited by 50 · see citing works
Wang, S., Qiu, M., Xia, W., Xu, Y., Mao, Q., Wang, J., Dong, G., Xu, L., Yang, X., & Yin, R. H. (2016) · Oncotarget · doi:10.18632/oncotarget.12945 · Cited by 50 · see citing works
Chen, X., Ding, G., Gao, Q., Sun, J., Zhang, Q., Du, L., Qiu, Z., Wang, C., Zheng, F., Sun, B., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0063093 · Cited by 46 · see citing works
Alpha B-crystallin is a new prognostic marker for laryngeal squamous cell carcinoma
Mao, Y., Zhang, D., Lin, H., Xiong, L., Liu, Y., Li, Q., Ma, J., Cao, Q., Chen, R., Zhu, J., et al. (2012) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-31-101 · Cited by 44 · see citing works
Effect of curcumin on Bcl-2 and Bax expression in nude mice prostate cancer.
Yang, J., Ning, J., Peng, L., & He, D. (2015) · PubMed Central · Cited by 44 · see citing works
Guo, L., Zhou, B. O., Liu, Z., Xu, Y., Lü, H., Xia, M., Guo, E., Shan, W., Chen, G., & Wang, C. (2016) · Tumor Biology · doi:10.1007/s13277-016-4984-3 · Cited by 42 · see citing works
Ginés, A., Bystrup, S., de Porras, V. R., Guardia, C., Musulén, E., Martínez‐Cardús, A., Manzano, J. L., Layos, L., Abad, A., & Martinez‐Balibrea, E. (2015) · PLoS ONE · doi:10.1371/journal.pone.0123830 · Cited by 37 · see citing works
Expression of glutamine metabolism-related proteins in thyroid cancer
Kim, H. M., Lee, Y. K., & Koo, J. S. (2016) · Oncotarget · doi:10.18632/oncotarget.10682 · Cited by 35 · see citing works
Ma, S., Jia, R., Li, D., & Shen, B. (2015) · BioMed Research International · doi:10.1155/2015/453986 · Cited by 32 · see citing works
Zhao, J., Zhou, R., Hui, K., Yang, Y., Zhang, Q., Ci, Y., Shi, L., Xu, C., Huang, F., & Hu, Y. (2016) · Oncotarget · doi:10.18632/oncotarget.13600 · Cited by 30 · see citing works
Self-citationLymphoma cells with increased anti-oxidant defenses acquire chemoresistance
Tome, M. E., Frye, J. B., Coyle, D. L., Jacobson, E. L., Samulitis, B. K., Dvorak, K., Dorr, R. T., & Briehl, M. M. (2012) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2012.487 · Cited by 29 · see citing works
Silencing of glutaminase 1 resensitizes Taxol-resistant breast cancer cells to Taxol
Fu, A., Yu, Z., Song, Y., & Zhang, E. (2015) · Molecular Medicine Reports · doi:10.3892/mmr.2015.3261 · Cited by 24 · see citing works
Mao, Y., Zhang, D., Wen, J., Cao, Q., Chen, R., Zhu, J., & Feng, Z. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms13022208 · Cited by 21 · see citing works
Dragon (RGMb) induces oxaliplatin resistance in colon cancer cells
Shi, Y., Huang, X., Chen, G.-B., Wang, Y., Zhi, Q., Liu, Y., Wu, X., Wang, L., Yang, B., Xiao, C., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.10338 · Cited by 18 · see citing works
Zhong, G., Li, H., Shan, T., & Zhang, N. (2015) · PubMed Central · Cited by 17 · see citing works
Knockdown of Nestin inhibits proliferation and migration of colorectal cancer cells.
Li, J., Wang, R., Yang, L., Wu, Q., Wang, Q., Nie, Z., Yu, Y., Ma, J., & Pan, Q. (2015) · Europe PMC (PubMed Central) · Cited by 17 · see citing works
A neutralized human LMP1-IgG inhibits ENKTL growth by suppressing the JAK3/STAT3 signaling pathway
Mao, Y., Wang, J., Zhang, M., Fan, W., Tang, Q., Xiong, S., Tang, X., Xu, J., Wang, L., Yang, S., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.14032 · Cited by 15 · see citing works
Self-citationLiang, X., Hou, S.-H., Li, Y., Wang, L., Zhang, X., & Yang, J. (2010) · PubMed · Cited by 14 · see citing works
RNA-seq identifies determinants of oxaliplatin sensitivity in colorectal cancer cell lines.
Li, X.-X., Peng, J.-J., Liang, L., Huang, L.-Y., Li, D.-W., Shi, D.-B., Zheng, H.-T., & Cai, S.-J. (2014) · PubMed Central · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Emerging therapies in cancer metabolism
Xiao, Y., Yu, T., Xu, Y., Ding, R., Wang, Y.-P., Jiang, Y., & Shao, Z. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.07.006 · Cited by 266 · see citing works
Dysregulation of glutaminase and glutamine synthetase in cancer
Matés, J. M., Campos-Sandoval, J. A., Santos-Jiménez, J. D. L., & Márquez, J. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.09.011 · Cited by 197 · see citing works
Hu, X., Ma, Z., Xu, B., Li, S., Yao, Z., Liang, B., Wang, J., Liao, W., Li, L., Wang, C., et al. (2023) · 癌症：英文版 · doi:10.1002/cac2.12459 · Cited by 116 · see citing works
Glycolysis-induced drug resistance in tumors—A response to danger signals?
Marcucci, F., & Rumio, C. (2021) · Neoplasia · doi:10.1016/j.neo.2020.12.009 · Cited by 113 · see citing works
PKM2, a potential target for regulating cancer
Li, Y., Li, X., Liu, J., Wang, H., Fan, L., Li, J., & Sun, G. (2018) · Gene · doi:10.1016/j.gene.2018.05.038 · Cited by 105 · see citing works
Gupta, A., Ajith, A., Singh, S., Panday, R. K., Samaiya, A., & Shukla, S. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0887-0 · Cited by 99 · see citing works
Protein kinase function of pyruvate kinase M2 and cancer
Chen, X., Chen, S., & Yu, D. (2020) · Cancer Cell International · doi:10.1186/s12935-020-01612-1 · Cited by 98 · see citing works
Targeting GLS1 to cancer therapy through glutamine metabolism
Yu, W., Yang, X., Zhang, Q., Sun, L., Yuan, S., & Xin, Y. (2021) · Clinical & Translational Oncology · doi:10.1007/s12094-021-02645-2 · Cited by 86 · see citing works
Tang, J., Ren, Y., Zhao, J., Long, F., Chen, J.-Y., & Jiang, Z. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.05.012 · Cited by 66 · see citing works
Gao, J., Zhao, Y., Li, T., Gan, X., & Yu, H. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/7702681 · Cited by 59 · see citing works
Yan, S., Zhou, N. Q., Zhang, D., Zhang, K., Zheng, W., Bao, Y., & Yang, W. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20215415 · Cited by 58 · see citing works
Wang, T., Cai, B., Ding, M., Su, Z., Liu, Y., & Shen, L. (2019) · The American Journal of the Medical Sciences · doi:10.1016/j.amjms.2019.05.014 · Cited by 47 · see citing works
Combined blockade of EGFR and glutamine metabolism in preclinical models of colorectal cancer
Cohen, A. S., Geng, L., Zhao, P., Fu, A., Schulte, M. L., Graves-Deal, R., Washington, M. K., Berlin, J., Coffey, R. J., & Manning, H. C. (2020) · Translational Oncology · doi:10.1016/j.tranon.2020.100828 · Cited by 49 · see citing works
“Two recent studies report the effects of genetic knockdown of GLS1 in CRC [26,27].”
BackgroundA Prognostic Model for Colon Cancer Patients Based on Eight Signature Autophagy Genes
Xu, J., Dai, S., Yuan, Y., Xiao, Q., & Ding, K. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.602174 · Cited by 47 · see citing works
Targeting pyruvate kinase muscle isoform 2 (PKM2) in cancer: What do we know so far?
Chhipa, A. S., & Patel, S. S. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119694 · Cited by 44 · see citing works
Cisplatin Resistance and Redox-Metabolic Vulnerability: A Second Alteration
Wangpaichitr, M., Theodoropoulos, G., Nguyen, D. J. M., Wu, C., Spector, S. A., Feun, L. G., & Savaraj, N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147379 · Cited by 44 · see citing works
Zheng, H., Zhang, M., Ke, X., Deng, X., Li, D., Wang, Q., Shanjun, Y., Xue, Y., & Wang, Q. (2020) · Cancer Biomarkers · doi:10.3233/cbm-201740 · Cited by 41 · see citing works
Metabolic Reprogramming of Cancer by Chemicals that Target Glutaminase Isoenzymes
Matés, J. M., Campos-Sandoval, J. A., Santos-Jiménez, J. D. L., Segura, J. A., Alonso, F. J., & Márquez, J. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867326666190416165004 · Cited by 40 · see citing works
The role of pyruvate kinase M2 in anticancer therapeutic treatments (Review)
Su, Q., Luo, S., Tan, Q., Deng, J., Zhou, S., Peng, M., Tao, T., & Yang, X. (2019) · Oncology Letters · doi:10.3892/ol.2019.10948 · Cited by 40 · see citing works
Hu, M., Liu, L., & Yao, W. (2018) · Gene · doi:10.1016/j.gene.2018.08.048 · Cited by 39 · see citing works
Papadaki, C., Manolakou, S. D., Lagoudaki, E. D., Pontikakis, S., Ierodiakonou, D., Vogiatzoglou, K., Messaritakis, I., Trypaki, M., Giannikaki, L., Sfakianaki, M., et al. (2020) · Cancers · doi:10.3390/cancers12041013 · Cited by 39 · see citing works
Targeting glutaminase-mediated glutamine dependence in papillary thyroid cancer
Yu, Y. W., Yu, X., Fan, C., Wang, H., Wang, R., Feng, C., & Guan, H. (2018) · Journal of Molecular Medicine · doi:10.1007/s00109-018-1659-0 · Cited by 38 · see citing works
MiR-138 Suppresses the PDK1 Expression to Decrease the Oxaliplatin Resistance of Colorectal Cancer
Wang, Y., Zhang, D., Yao, L., & Fang, F. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s242929 · Cited by 37 · see citing works
Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance
Manna, D., & Sarkar, D. (2021) · Cancers · doi:10.3390/cancers13081792 · Cited by 38 · see citing works
Amrutkar, M., Berg, K., Balto, A., Skilbrei, M. G., Finstadsveen, A. V., Aasrum, M., Gladhaug, I. P., & Verbeke, C. S. (2023) · Cancer Cell International · doi:10.1186/s12935-023-02852-7 · Cited by 32 · see citing works
Hashemi, M., Esbati, N., Rashidi, M., Gholami, S., Raesi, R., Bidoki, S. S., Goharrizi, M. A. S. B., Motlagh, Y. S. M., Khorrami, R., Tavakolpournegari, A., et al. (2023) · Translational Oncology · doi:10.1016/j.tranon.2023.101846 · Cited by 31 · see citing works
Targeting glutaminase 1 (GLS1) by small molecules for anticancer therapeutics
Chen, Y., Tan, L., Gao, J., Lin, C., Wu, F., Li, Y., & Zhang, J. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115306 · Cited by 29 · see citing works
PKM2 Expression as Biomarker for Resistance to Oxaliplatin-Based Chemotherapy in Colorectal Cancer
Sfakianaki, M., Papadaki, C., Tzardi, M. N., Trypaki, M., Manolakou, S. D., Messaritakis, I., Saridaki, Z., Athanasakis, E., Mavroudis, D., Tsiaoussis, J., et al. (2020) · Cancers · doi:10.3390/cancers12082058 · Cited by 28 · see citing works
Wang, X., Xiao-xia, Y., Peng-Fei, S., Zong-Xue, Z., & Xiu-li, G. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175323 · Cited by 23 · see citing works
Glutaminase - A potential target for cancer treatment
Josephine, A., Varalakshmi, S., Sekar, A. K., Devarajan, N., Janakiraman, B., & Rajendran, P. (2024) · Biomedicine · doi:10.37796/2211-8039.1445 · Cited by 17 · see citing works
Oncogenic Role of Exosomal Circular and Long Noncoding RNAs in Gastrointestinal Cancers
Yun, B. D., Choi, Y. J., Son, S. W., Cipolla, G. A., Berti, F. C. B., Malheiros, D., Oh, T., Kuh, H. J., Choi, S. Y., & Park, J. K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020930 · Cited by 14 · see citing works
Wu, G., Li, T., Chen, Y., Ye, S., Zhou, S., Tian, X., Anwaier, A., Zhu, S., Xu, W., Hao, X., et al. (2024) · Clinical and Experimental Medicine · doi:10.1007/s10238-024-01390-4 · Cited by 14 · see citing works
Tumor pyruvate kinase M2: A promising molecular target of gastrointestinal cancer
Chen, G., Guan, L., Hou, J., Deng, X., Ao, S., Li, Z., & Lyu, G. (2018) · Chinese Journal of Cancer Research · doi:10.21147/j.issn.1000-9604.2018.06.11 · Cited by 12 · see citing works
Liu, Z., Fan, L., Niu, D., Chen, M., Zhang, W., Liu, Y., Xu, J., & Wang, D. (2023) · Oncology Reports · doi:10.3892/or.2023.8607 · Cited by 11 · see citing works
Colombo, M., Platonova, N., Giannandrea, D., Palano, M. T., Basile, A., & Chiaramonte, R. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00145 · Cited by 11 · see citing works
Chen, J., Wang, H., & Tang, M. (2023) · Journal of Chemotherapy · doi:10.1080/1120009x.2023.2253680 · Cited by 8 · see citing works
The role and therapeutic potential of glucose metabolism in multidrug resistance of cancer
Wang, Q., Li, K., Li, L., Qin, L., Qi, Y., Liu, K., Yuan, H., & Lin, P. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1584630 · Cited by 8 · see citing works
Cheng, Q., Chen, Y., Zou, D., Li, Q., Shi, X., Qin, Q., Liu, M., Wang, L., & Wang, Z. (2024) · Advanced Science · doi:10.1002/advs.202409329 · Cited by 7 · see citing works
Quantitative proteomic analysis of oxaliplatin induced peripheral neurotoxicity
Yang, L., Wang, H., Lu, W., Yang, G., Lin, Z., Chen, R., & Li, H. (2022) · Journal of Proteomics · doi:10.1016/j.jprot.2022.104682 · Cited by 7 · see citing works
Self-citationXiao, S., Xu, G., Wang, Z., & Chong, T. (2021) · Oncology Reports · doi:10.3892/or.2021.8165 · Cited by 6 · see citing works
Leveraging cancer metabolism to translate into effective therapeutics
Xu, J., Guo, L., Wang, Y., Li, X., Yi, P., & Cheng, C. (2025) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2025.12.003 · Cited by 3 · see citing works
Liu, Z., Fan, L., Niu, D., Chen, M., Zhang, W., Xu, J., & Wang, D. (2022) · Research Square · doi:10.21203/rs.3.rs-2290126/v1 · Cited by 2 · see citing works
Shen, J., Yu, M., Luo, J., Tang, X., Han, Z., Luo, W., Xie, F., Cao, M., Zhou, T., & He, J. (2023) · PeerJ · doi:10.7717/peerj.16297
Amrutkar, M., Berg, K., Balto, A., Skilbrei, M. G., Finstadsveen, A. V., Aasrum, M., Gladhaug, I. P., & Verbeke, C. S. (2024) · Figshare · doi:10.6084/m9.figshare.26562625
Amrutkar, M., Berg, K., Balto, A., Skilbrei, M. G., Finstadsveen, A. V., Aasrum, M., Gladhaug, I. P., & Verbeke, C. S. (2024) · Figshare · doi:10.6084/m9.figshare.26562631
Amrutkar, M., Berg, K., Balto, A., Skilbrei, M. G., Finstadsveen, A. V., Aasrum, M., Gladhaug, I. P., & Verbeke, C. S. (2024) · Figshare · doi:10.6084/m9.figshare.26562628
Amrutkar, M., Berg, K., Balto, A., Skilbrei, M. G., Finstadsveen, A. V., Aasrum, M., Gladhaug, I. P., & Verbeke, C. S. (2024) · Figshare · doi:10.6084/m9.figshare.26562622
Belluti, S., Mularoni, V., Iseppato, N., Campani, V., Ronzio, M., Righi, V., Cuoghi, L., Rinaldi, A., Martinelli, T., Cani, O., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.03.708979
Ou, M., Liu, Y., Luo, R., Cao, J., Miao, R., Li, W., Wang, X., Fu, Y., & Mei, L. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.115156
BindingDB (2024) · UC San Diego · doi:10.7270/q2h999mk
- Authors
- Lu, W.-Q., Hu, Y.-Y., Lin, X.-P., & Fan, W.
- Affiliations
- Sun Yat-sen University Cancer Center (CN)
- Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
- Corresponding author
- Fan, Wei
- ORCID
- Fan, Wei
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2017-04-24
- Volume
- 8
- Issue
- 27
- Pages
- 44171-44185
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC5546471
- OpenAlex
- W2608485495
- Cited by
- 49
- References
- 46
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 6
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Health Medical Collaborative Innovation Program of Guangzhou (201400000001, No. 201400000001)
- Guangzhou Municipal Science and Technology Project
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- PKM2, GLS1, oxaliplatin resistance, colorectal cancer, aerobic glycolysis, glutaminolysis, P-glycoprotein, apoptosis, tumor growth, xenografts, drug resistance reversal, gene knockdown, cell migration and invasion, tumor angiogenesis, tumor microenvironment, tumor-infiltrating immune cells
- MeSH terms
- Oxaliplatin, Thyroid Hormone-Binding Proteins, Animals, Antineoplastic Agents, Carrier Proteins, Cell Survival, Disease Models, Animal, Glutaminase, Humans, Immunohistochemistry, Membrane Proteins, Organoplatinum Compounds, Phenotype, Thyroid Hormones, Colorectal Neoplasms, Gene Expression, Gene Expression Regulation, Neoplastic, Drug Resistance, Neoplasm, ATP Binding Cassette Transporter, Subfamily B, Member 1, Xenograft Model Antitumor Assays, Cell Line, Tumor, Tumor Burden, Mice, Gene Knockdown Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
