|
|
XIAP Mediated-PTEN Neddylation Promotes Proliferation and Migration of Colon Cancer Cells |
YUAN Shu-hui1,3,LI Shao-hua2,FANG Wei2,PENG Zhi-qiang3,ZHANG Ling-qiang1,3,**() |
1 School of Basic Medicine, Qingdao 266071, China 2 Shanghai Fengxian Central Hospital, The Third School of Clinical Medicine, Southern Medical University, Shanghai 201499, China 3 State Key Laboratory of Proteomics, Beijing National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 100850, China |
|
|
Abstract Objective: To explore the functional role of XIAP-PTEN neddylation axis in colorectal cancer at cell line and clinical level. Methods: The expression level of XIAP was analyzed in tissue microarray of colorectal cancer by immunohistochemical staining, and the protein level of XIAP was detected in human colorectal cancer and adjacent normal tissues by Western blot. Co-IP was performed to analyze the interaction between endogenous PTEN and XIAP in SW480 cell line. CRISPR Cas9 technology was used to construct XIAP-knockout SW480 cell line, and the neddylation level of PTEN was analyzed in sg-XIAP cells by immunoprecipitation and Western blot. XIAP knockout or wild type SW480 cell lines were co-transfected with FLAG-Vector or FLAG-PTEN-Nedd8 plasmid, and then CCK8 and Transwell experiments were used to assay the proliferation and migration of XIAP-PTEN neddylation axis in SW480 cells, respectively. Results: The expression levels of XIAP were up-regulated in colon and rectum cancer tissues compared with adjacent normal tissues. XIAP interacted with PTEN in SW480 colon cancer cells. Deletion of XIAP inhibited PTEN neddylation in SW480 cells. The level of PTEN neddylation was elevated in colorectal cancer tissues compared with adjacent normal tissues. Deletion of XIAP inhibited the proliferation and migration of SW480 cells significantly, while PTEN-Nedd8 fusion protein rescued the phenotypes of XIAP deletion in SW480 cells. Conclusion: XIAP-PTEN neddylation axis promotes SW480 colon cancer cell proliferation and migration.
|
Received: 19 December 2021
Published: 17 June 2022
|
|
Corresponding Authors:
Ling-qiang ZHANG
E-mail: zhanglq@nic.bmi.ac.cn
|
|
|
[1] |
Cao M M, Li H, Sun D Q, et al. Cancer burden of major cancers in China: a need for sustainable actions. Cancer Communications, 2020, 40(5): 205-210.
doi: 10.1002/cac2.12025
|
|
|
[2] |
Siegel R L, Miller K D, Jemal A. Cancer statistics, 2020. CA: A Cancer Journal for Clinicians, 2020, 70(1): 7-30.
doi: 10.3322/caac.21590
|
|
|
[3] |
Sansom O J, Meniel V, Wilkins J A, et al. Loss of Apc allows phenotypic manifestation of the transforming properties of an endogenous K-ras oncogene in vivo. Proceedings of the National Academy of Sciences of the United States of America, 2006, 103(38): 14122-14127.
|
|
|
[4] |
Chen J, Guo F, Shi X, et al. BRAF V600E mutation and KRAS Codon 13 mutations predict poor survival in Chinese colorectal cancer patients. BMC Cancer, 2014, 14: 802.
doi: 10.1186/1471-2407-14-802
|
|
|
[5] |
Alitalo K, Schwab M, Lin C C, et al. Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. Proceedings of the National Academy of Sciences of the United States of America, 1983, 80(6): 1707-1711.
|
|
|
[6] |
Ashton-Rickardt P G, Dunlop M G, Nakamura Y, et al. High frequency of APC loss in sporadic colorectal carcinoma due to breaks clustered in 5q21-22. Oncogene, 1989, 4(10): 1169-1174.
pmid: 2797819
|
|
|
[7] |
Muzny D M, Bainbridge M N, Chang K, et al. Comprehensive molecular characterization of human colon and rectal cancer. Nature, 2012, 487 (7407): 330-337.
doi: 10.1038/nature11252
|
|
|
[8] |
Nishisho I, Nakamura Y, Miyoshi Y, et al. Mutations of chromosome 5q 21 genes in FAP and colorectal cancer patients. Science, 1991, 253(5020): 665-669.
doi: 10.1126/science.1651563
pmid: 1651563
|
|
|
[9] |
Wang Y, Cao Y, Huang X, et al. Allele-specific expression of mutated in colorectal cancer (MCC) gene and alternative susceptibility to colorectal cancer in schizophrenia. Scientific Reports, 2016, 6: 26688.
doi: 10.1038/srep26688
|
|
|
[10] |
Akkiprik M, Ataizi-Celikel C, Düᶊünceli F, et al. Clinical significance of p53, K-ras and DCC gene alterations in the stage I-II colorectal cancers. Journal of Gastrointestinal and Liver Diseases: JGLD, 2007, 16(1): 11-17.
|
|
|
[11] |
Djansugurova L, Zhunussova G, Khussainova E, et al. Association of DCC, MLH1, GSTT1, GSTM1, and TP53 gene polymorphisms with colorectal cancer in Kazakhstan. Tumor Biology, 2015, 36(1): 279-289.
doi: 10.1007/s13277-014-2641-2
|
|
|
[12] |
Kleivi K, Lind G E, Diep C B, et al. Gene expression profiles of primary colorectal carcinomas, liver metastases, and carcinomatoses. Molecular Cancer, 2007, 6: 2.
doi: 10.1186/1476-4598-6-2
|
|
|
[13] |
Markowitz S D, Bertagnolli M M. Molecular origins of cancer: molecular basis of colorectal cancer. The New England Journal of Medicine, 2009, 361(25): 2449-2460.
doi: 10.1056/NEJMra0804588
pmid: 20018966
|
|
|
[14] |
Álvarez-Garcia V, Tawil Y, Wise H M, et al. Mechanisms of PTEN loss in cancer: It’s all about diversity. Seminars in Cancer Biology, 2019, 59: 66-79.
doi: S1044-579X(18)30059-2
pmid: 30738865
|
|
|
[15] |
Song M S, Salmena L, Pandolfi P P. The functions and regulation of the PTEN tumour suppressor. Nature Reviews Molecular Cell Biology, 2012, 13(5): 283-296.
doi: 10.1038/nrm3330
pmid: 22473468
|
|
|
[16] |
Okumura K, Mendoza M, Bachoo R M, et al. PCAF modulates PTEN activity. Journal of Biological Chemistry, 2006, 281(36): 26562-26568.
doi: 10.1074/jbc.M605391200
pmid: 16829519
|
|
|
[17] |
Trotman L C, Wang X J, Alimonti A, et al. Ubiquitination regulates PTEN nuclear import and tumor suppression. Cell, 2007, 128(1): 141-156.
doi: 10.1016/j.cell.2006.11.040
pmid: 17218261
|
|
|
[18] |
van Themsche C, Leblanc V, Parent S, et al. X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization. Journal of Biological Chemistry, 2009, 284(31): 20462-20466.
doi: 10.1074/jbc.C109.009522
pmid: 19473982
|
|
|
[19] |
Maddika S, Kavela S, Rani N, et al. WWP2 is an E3 ubiquitin ligase for PTEN. Nature Cell Biology, 2011, 13 (6): 728-733.
doi: 10.1038/ncb2240
|
|
|
[20] |
Xu W T, Yang Z, Zhou S F, et al. Posttranslational regulation of phosphatase and tensin homolog (PTEN) and its functional impact on cancer behaviors. Drug Design, Development and Therapy, 2014, 8: 1745-1751.
|
|
|
[21] |
Xie P, Peng Z, Chen Y, et al. Neddylation of PTEN regulates its nuclear import and promotes tumor development. Cell Research, 2021, 31 (3): 291-311.
doi: 10.1038/s41422-020-00443-z
|
|
|
[22] |
Xirodimas D P. Novel substrates and functions for the ubiquitin-like molecule NEDD8. Biochemical Society Transactions, 2008, 36(5): 802-806.
doi: 10.1042/BST0360802
|
|
|
[23] |
Pan Z Q, Kentsis A, Dias D C, et al. Nedd8 on cullin: building an expressway to protein destruction. Oncogene, 2004, 23 (11): 1985-1997.
doi: 10.1038/sj.onc.1207414
|
|
|
[24] |
Huang D T, Ayrault O, Hunt H W, et al. E2-RING expansion of the NEDD 8 cascade confers specificity to cullin modification. Molecular Cell, 2009, 33(4): 483-495.
doi: 10.1016/j.molcel.2009.01.011
|
|
|
[25] |
Xirodimas D P, Saville M K, Bourdon J C, et al. Mdm2-mediated NEDD 8 conjugation of p53 inhibits its transcriptional activity. Cell, 2004, 118(1): 83-97.
pmid: 15242646
|
|
|
[26] |
Watson I R, Blanch A, Lin D C C, et al. Mdm2-mediated NEDD 8 modification of TAp73 regulates its transactivation function. Journal of Biological Chemistry, 2006, 281(45): 34096-34103.
doi: 10.1074/jbc.M603654200
pmid: 16980297
|
|
|
[27] |
Stickle N H, Chung J, Klco J M, et al. pVHL modification by NEDD 8 is required for fibronectin matrix assembly and suppression of tumor development. Molecular and Cellular Biology, 2004, 24(8): 3251-3261.
doi: 10.1128/MCB.24.8.3251-3261.2004
|
|
|
[28] |
Jiang Y N, Jia L J. Neddylation pathway as a novel anti-cancer target: mechanistic investigation and therapeutic implication. Anti-Cancer Agents in Medicinal Chemistry, 2015, 15(9): 1127-1133.
doi: 10.2174/1871520615666150305111257
|
|
|
[29] |
Gai W B, Peng Z Q, Liu C H, et al. Advances in cancer treatment by targeting the neddylation pathway. Frontiers in Cell and Developmental Biology, 2021, 9: 653882.
doi: 10.3389/fcell.2021.653882
|
|
|
[30] |
Zhou L S, Jiang Y Y, Luo Q, et al. Neddylation: a novel modulator of the tumor microenvironment. Molecular Cancer, 2019, 18(1): 77.
doi: 10.1186/s12943-019-0979-1
|
|
|
[31] |
Soucy T A, Smith P G, Milhollen M A, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature, 2009, 458 (7239): 732-736.
doi: 10.1038/nature07884
|
|
|
[32] |
Sumi H, Inazuka M, Morimoto M, et al. An inhibitor of apoptosis protein antagonist T-3256336 potentiates the antitumor efficacy of the Nedd8-activating enzyme inhibitor pevonedistat (TAK-924/MLN4924). Biochemical and Biophysical Research Communications, 2016, 480(3): 380-386.
doi: 10.1016/j.bbrc.2016.10.058
|
|
|
[33] |
Oladghaffari M, Shabestani Monfared A, Farajollahi A, et al. MLN4924 and 2DG combined treatment enhances the efficiency of radiotherapy in breast cancer cells. International Journal of Radiation Biology, 2017, 93(6): 590-599.
doi: 10.1080/09553002.2017.1294272
pmid: 28291374
|
|
|
[34] |
Snaebjornsson M T, Janaki-Raman S, Schulze A. Greasing the wheels of the cancer machine: the role of lipid metabolism in cancer. Cell Metabolism, 2020, 31(1): 62-76.
doi: S1550-4131(19)30617-5
pmid: 31813823
|
|
|
[35] |
Xie P, Zhang M, He S, et al. The covalent modifier Nedd 8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis. Nature Communications, 2014, 5: 3733.
doi: 10.1038/ncomms4733
|
|
|
[36] |
Zhou L S, Zhang W J, Sun Y, et al. Protein neddylation and its alterations in human cancers for targeted therapy. Cellular Signalling, 2018, 44: 92-102.
doi: 10.1016/j.cellsig.2018.01.009
|
|
|
[37] |
Wan J F, Zhu J, Li G C, et al. Radiosensitization of human colorectal cancer cells by MLN4924: an inhibitor of NEDD8-activating enzyme. Technology in Cancer Research & Treatment, 2016, 15(4): 527-534.
|
|
|
[38] |
Currie E, Schulze A, Zechner R, et al. Cellular fatty acid metabolism and cancer. Cell Metabolism, 2013, 18(2): 153-161.
doi: 10.1016/j.cmet.2013.05.017
pmid: 23791484
|
|
|
[39] |
Beyaz S, Mana M D, Roper J, et al. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature, 2016, 531 (7592): 53-58.
doi: 10.1038/nature17173
|
|
|
[40] |
Zaytseva Y Y, Harris J W, Mitov M I, et al. Increased expression of fatty acid synthase provides a survival advantage to colorectal cancer cells via upregulation of cellular respiration. Oncotarget, 2015, 6(22): 18891-18904.
doi: 10.18632/oncotarget.3783
|
|
|
[41] |
Wang H Y, Xi Q L, Wu G H. Fatty acid synthase regulates invasion and metastasis of colorectal cancer via Wnt signaling pathway. Cancer Medicine, 2016, 5(7): 1599-1606.
doi: 10.1002/cam4.711
|
|
|
[42] |
Tu H L, Costa M. XIAP’s profile in human cancer. Biomolecules, 2020, 10(11): 1493.
doi: 10.3390/biom10111493
|
|
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
|
Shared |
|
|
|
|
|
Discussed |
|
|
|
|