Generic placeholder image

Current Proteomics


ISSN (Print): 1570-1646
ISSN (Online): 1875-6247

Research Article

Analysis of Oxaliplatin Resistance in Colorectal Cancer Cells by Combined Proteomics and Phosphoproteomic

Author(s): Rui Yang, Kunli Feng, Yanhong Cao, Hao Wang and Baolong Wang*

Volume 18, Issue 2, 2021

Published on: 25 February, 2020

Page: [193 - 203] Pages: 11

DOI: 10.2174/1570164617666200225123903

Price: $65


Background: Oxaliplatin(Oxa) is a major chemotherapy drug for colorectal cancer. However, drug resistance is a major cause of treatment failure for late-stage colorectal cancer. Therefore, it is necessary to explore the mechanism of resistance to oxaliplatin in HCT116 colorectal cancer cells.

Objective: Therefore, this study explored the mechanisms of HCT116 cells resistance to oxaliplatin by combining the results of proteomic and phosphoproteomic analyses.

Methods: In this study, firstly,we constructed oxaliplatin-resistant HCT116 cells called HCT116/ Oxa. Then, we conducted a quantitative study of phosphoproteomics in HCT116 and HCT116/ Oxa cells via TMT labeling, bio-material-based PTM enrichment, HPLC fractionation, and LC-MS/MS analyses. At the same time, we applied TMT/iTRAQ labeling, HPLC fractionation, and LC-MS/MS to conduct proteomic and phosphoproteomic analyses of the cell lines. Finally, we analyzed the results from Gene Ontology (GO), protein domain, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using the 1.5 change rate as a meaningful change threshold.

Results: Our analysis confirmed the previously described mechanisms of colon cancer resistance and revealed the important role of phosphorylation in drug resistance.

Conclusion: Collectively, this study provides a new direction for the study of oxaliplatin resistance in colorectal cancer.

Keywords: Drug resistance, oxaliplatin, proteomic, phosphoproteomic, colorectal cancer, phosphorylation.

Graphical Abstract
Yue, B.; Liu, C.; Sun, H.; Liu, M.; Song, C.; Cui, R.; Qiu, S.; Zhong, M. A positive feed-forward loop between LncRNA-CYTOR and Wnt/β-Catenin signaling promotes metastasis of colon cancer. Mol. Ther., 2018, 26(5), 1287-1298.
[] [PMID: 29606502]
Hsu, H.H.; Chen, M.C.; Baskaran, R.; Lin, Y.M.; Day, C.H.; Lin, Y.J.; Tu, C.C.; Vijaya Padma, V.; Kuo, W.W.; Huang, C.Y. Oxaliplatin resistance in colorectal cancer cells is mediated via activation of ABCG2 to alleviate ER stress induced apoptosis. J. Cell. Physiol., 2018, 233(7), 5458-5467.
[] [PMID: 29247488]
Skarkova, V.; Kralova, V.; Krbal, L.; Matouskova, P.; Soukup, J.; Rudolf, E. Oxaliplatin and irinotecan induce heterogenous changes in the EMT markers of metastasizing colorectal carcinoma cells. Exp. Cell Res., 2018, 369(2), 295-303.
[] [PMID: 29842879]
Wilson, T.R.; Longley, D.B.; Johnston, P.G. Chemoresistance in solid tumours. Ann. Oncol., 2006, 17(Suppl. 10), x315-x324.
[] [PMID: 17018746]
Hammond, W.A.; Swaika, A.; Mody, K. Pharmacologic resistance in colorectal cancer: a review. Ther. Adv. Med. Oncol., 2016, 8(1), 57-84.
[] [PMID: 26753006]
Longley, D.B.; Johnston, P.G. Molecular mechanisms of drug resistance. J. Pathol., 2005, 205(2), 275-292.
[] [PMID: 15641020]
Martinez-Balibrea, E.; Martínez-Cardús, A.; Ginés, A.; Ruiz de Porras, V.; Moutinho, C.; Layos, L.; Manzano, J.L.; Bugés, C.; Bystrup, S.; Esteller, M.; Abad, A. Tumor-related molecular mechanisms of oxaliplatin resistance. Mol. Cancer Ther., 2015, 14(8), 1767-1776.
[] [PMID: 26184483]
Afrin, S.; Giampieri, F.; Forbes-Hernández, T.Y.; Gasparrini, M.; Amici, A.; Cianciosi, D.; Quiles, J.L.; Battino, M. Manuka honey synergistically enhances the chemopreventive effect of 5-fluorouracil on human colon cancer cells by inducing oxidative stress and apoptosis, altering metabolic phenotypes and suppressing metastasis ability. Free Radic. Biol. Med., 2018, 126, 41-54.
[] [PMID: 30056083]
Roy, S.; Majumdar, A.P. Signaling in colon cancer stem cells. J. Mol. Signal., 2012, 7(1), 11.
[] [PMID: 22866952]
Saif, M.W.; Chu, E. Biology of colorectal cancer. Cancer J., 2010, 16(3), 196-201.
[] [PMID: 20526096]
Liao, X.; Song, G.; Xu, Z.; Bu, Y.; Chang, F.; Jia, F.; Xiao, X.; Ren, X.; Zhang, M.; Jia, Q. Oxaliplatin resistance is enhanced by saracatinib viaupregulation Wnt-ABCG1 signaling in hepatocellular carcinoma. BMC Cancer, 2020, 20(1), 31.
[] [PMID: 31931755]
Shen, Z.; Wang, B.; Luo, J.; Jiang, K.; Zhang, H.; Mustonen, H.; Puolakkainen, P.; Zhu, J.; Ye, Y.; Wang, S. Global-scale profiling of differential expressed lysine acetylated proteins in colorectal cancer tumors and paired liver metastases. J. Proteomics, 2016, 142, 24-32.
[] [PMID: 27178108]
Ruprecht, B.; Zaal, E.A.; Zecha, J.; Wu, W.; Berkers, C.R.; Kuster, B.; Lemeer, S. Lapatinib resistance in breast cancer cells is accompanied by phosphorylation-mediated reprogramming of glycolysis. Cancer Res., 2017, 77(8), 1842-1853.
[] [PMID: 28209619]
Lazarova, D.L.; Bordonaro, M. Vimentin, colon cancer progression and resistance to butyrate and other HDACis. J. Cell. Mol. Med., 2016, 20(6), 989-993.
[] [PMID: 27072512]
Zhou, Y.; Wang, L.; Ban, X.; Zeng, T.; Zhu, Y.; Li, M.; Guan, X.Y.; Li, Y. DHRS2 inhibits cell growth and motility in esophageal squamous cell carcinoma. Oncogene, 2018, 37(8), 1086-1094.
[] [PMID: 29106393]
Chillemi, G.; D’Annessa, I.; Fiorani, P.; Losasso, C.; Benedetti, P.; Desideri, A. Thr729 in human topoisomerase I modulates anti-cancer drug resistance by altering protein domain communications as suggested by molecular dynamics simulations. Nucleic Acids Res., 2008, 36(17), 5645-5651.
[] [PMID: 18765473]
Izaurralde, E.; Lewis, J.; McGuigan, C.; Jankowska, M.; Darzynkiewicz, E.; Mattaj, I.W. A nuclear cap binding protein complex involved in pre-mRNA splicing. Cell, 1994, 78(4), 657-668.
[] [PMID: 8069914]
Izaurralde, E.; Lewis, J.; Gamberi, C.; Jarmolowski, A.; McGuigan, C.; Mattaj, I.W. A cap-binding protein complex mediating U snRNA export. Nature, 1995, 376(6542), 709-712.
[] [PMID: 7651522]
Ishigaki, Y.; Li, X.; Serin, G.; Maquat, L.E. Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20. Cell, 2001, 106(5), 607-617.
[] [PMID: 11551508]
Nakajima, K.; Hirose, H.; Taniguchi, M.; Kurashina, H.; Arasaki, K.; Nagahama, M.; Tani, K.; Yamamoto, A.; Tagaya, M. Involvement of BNIP1 in apoptosis and endoplasmic reticulum membrane fusion. EMBO J., 2004, 23(16), 3216-3226.
[] [PMID: 15272311]
Sivaram, M.V.; Wadzinski, T.L.; Redick, S.D.; Manna, T.; Doxsey, S.J. Dynein light intermediate chain 1 is required for progress through the spindle assembly checkpoint. EMBO J., 2009, 28(7), 902-914.
[] [PMID: 19229290]
Kukcinaviciute, E.; Jonusiene, V.; Sasnauskiene, A.; Dabkeviciene, D.; Eidenaite, E.; Laurinavicius, A. Significance of Notch and Wnt signaling for chemoresistance of colorectal cancer cells HCT116. J. Cell. Biochem., 2018, 119(7), 5913-5920.
[] [PMID: 29637602]
Lee, W.Y.; Kuo, C.C.; Lin, B.X.; Cheng, C.H.; Chen, K.C.; Lin, C.W. Podocalyxin-like protein 1 regulates TAZ signaling and stemness properties in colon cancer. Int. J. Mol. Sci., 2017, 18(10), E2047.
[] [PMID: 28946619]
Schönle, A.; Hartl, F.A.; Mentzel, J.; Nöltner, T.; Rauch, K.S.; Prestipino, A.; Wohlfeil, S.A.; Apostolova, P.; Hechinger, A.K.; Melchinger, W.; Fehrenbach, K.; Guadamillas, M.C.; Follo, M.; Prinz, G.; Ruess, A.K.; Pfeifer, D.; del Pozo, M.A.; Schmitt-Graeff, A.; Duyster, J.; Hippen, K.I.; Blazar, B.R.; Schachtrup, K.; Minguet, S.; Zeiser, R. Caveolin-1 regulates TCR signal strength and regulatory T-cell differentiation into alloreactive T cells. Blood, 2016, 127(15), 1930-1939.
[] [PMID: 26837700]
Hwangbo, C.; Tae, N.; Lee, S.; Kim, O.; Park, O.K.; Kim, J.; Kwon, S.H.; Lee, J.H. Syntenin regulates TGF-β1-induced Smad activation and the epithelial-to-mesenchymal transition by inhibiting caveolin-mediated TGF-β type I receptor internalization. Oncogene, 2016, 35(3), 389-401.
[] [PMID: 25893292]
Deisenroth, C.; Thorner, A.R.; Enomoto, T.; Perou, C.M.; Zhang, Y. Mitochondrial Hep27 is a c-Myb target gene that inhibits Mdm2 and stabilizes p53. Mol. Cell. Biol., 2010, 30(16), 3981-3993.
[] [PMID: 20547751]
Shafqat, N.; Shafqat, J.; Eissner, G.; Marschall, H.U.; Tryggvason, K.; Eriksson, U.; Gabrielli, F.; Lardy, H.; Jörnvall, H.; Oppermann, U. Hep27, a member of the short-chain dehydrogenase/reductase family, is an NADPH-dependent dicarbonyl reductase expressed in vascular endothelial tissue. Cell. Mol. Life Sci., 2006, 63(10), 1205-1213.
[] [PMID: 16685466]
Vasquez-Del Carpio, R.; Kaplan, F.M.; Weaver, K.L.; VanWye, J.D.; Alves-Guerra, M.C.; Robbins, D.J.; Capobianco, A.J. Assembly of a Notch transcriptional activation complex requires multimerization. Mol. Cell. Biol., 2011, 31(7), 1396-1408.
[] [PMID: 21245387]
Zhang, X.; Yan, C.; Hang, J.; Finci, L.I.; Lei, J.; Shi, Y. An atomic structure of the human spliceosome. Cell, 2017, 169(5), 918-929.e14.
[] [PMID: 28502770]
Piccolo, S.; Dupont, S.; Cordenonsi, M. The biology of YAP/TAZ: hippo signaling and beyond. Physiol. Rev., 2014, 94(4), 1287-1312.
[] [PMID: 25287865]
Tumaneng, K.; Schlegelmilch, K.; Russell, R.C.; Yimlamai, D.; Basnet, H.; Mahadevan, N.; Fitamant, J.; Bardeesy, N.; Camargo, F.D.; Guan, K.L. YAP mediates crosstalk between the Hippo and PI(3)K-TOR pathways by suppressing PTEN via miR-29. Nat. Cell Biol., 2012, 14(12), 1322-1329.
[] [PMID: 23143395]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy