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Cited by 22Cytokine Signaling Pathways and InteractionsGlioma Diagnosis and TreatmentProtein Tyrosine Phosphatases

SHF Acts as a Novel Tumor Suppressor in Glioblastoma Multiforme by Disrupting STAT3 Dimerization

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Wang, Jingjing, Huang, Zixuan, Ji, Li, Chen, Cheng, Wan, Quan, Xin, Yu, Pu, Zhening, Li, Koukou +11 more·2022·Advanced Science
DOI 10.1002/advs.202200169PMC PMC9475553
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Abstract

Sustained activation of signal transducer and activator of transcription 3 (STAT3) is a critical contributor in tumorigenesis and chemoresistance, thus making it an attractive cancer therapeutic target. Here, SH2 domain‐containing adapter protein F (SHF) is identified as a tumor suppressor in glioblastoma Multiforme (GBM) and its negative regulation of STAT3 activity is characterized. Mechanically, SHF selectively binds and inhibits acetylated STAT3 dimerization without affecting STAT3 phosphorylation or acetylation. Additionally, by blocking STAT3‐DNMT1 (DNA Methyltransferase 1) interaction, SHF relieves methylation of tumor suppressor genes. The SH2 domain is documented to be essential for SHF's actions on STAT3, and almost entirely replaces the functions of SHF on STAT3 independently. Moreover, the peptide C16 a peptide derived from the STAT3‐binding sites of SHF inhibits STAT3 dimerization and STAT3/DNMT1 interaction, and achieves remarkable growth inhibition in GBM cells in vitro and in vivo. These findings strongly identify targeting of the SHF/STAT3 interaction as a promising strategy for developing an optimal STAT3 inhibitor and provide early evidence of the potential clinical efficacy of STAT3 inhibitors such as C16 in GBM.

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  1. [1]T. Kanderi, V. Gupta, Glioblastoma Multiforme, StatPearls, Treasure Island, FL 2021. 32644380
  2. [2]A. Ou, M. Ott, D. Fang, A. B. Heimberger, Cancers (Basel) 2021, 13, 437. 33498872 PMC7865703
  3. [3]A. Tesoriere, A. Dinarello, F. Argenton, Biomedicines 2021, 9, 956. 34440160 PMC8393524
  4. [4]G. Sethi, S. Chatterjee, P. Rajendran, F. Li, M. K. Shanmugam, K. F. Wong, A. P. Kumar, P. Senapati, A. K. Behera, K. M. Hui, J. Basha, N. Natesh, J. M. Luk, T. K. Kundu, Mol. Cancer 2014, 13, 66. 24655440 PMC3998115
  5. [5]X. Zhang, Y. Sun, R. Pireddu, H. Yang, M. K. Urlam, H. R. Lawrence, W. C. Guida, N. J. Lawrence, S. M. Sebti, Cancer Res. 2013, 73, 1922. 23322008 PMC4030628
  6. [6]Z. L. Yuan, Y. J. Guan, D. Chatterjee, Y. E. Chin, Science 2005, 307, 269. 15653507
  7. [7]L. Bai, H. Zhou, R. Xu, Y. Zhao, K. Chinnaswamy, D. McEachern, J. Chen, C. Y. Yang, Z. Liu, M. Wang, L. Liu, H. Jiang, B. Wen, P. Kumar, J. L. Meagher, D. Sun, J. A. Stuckey, S. Wang, Cancer Cell 2019, 36, 498. 31715132 PMC6880868
  8. [8]R. A. Cerulli, L. Shehaj, I. Tosic, K. Jiang, J. Wang, D. A. Frank, J. A. Kritzer, Bioorg. Med. Chem. 2020, 28, 115542. 32503696 PMC7294595
  9. [9]M. Huang, K. Song, X. Liu, S. Lu, Q. Shen, R. Wang, J. Gao, Y. Hong, Q. Li, D. Ni, J. Xu, G. Chen, J. Zhang, Nucleic Acids Res. 2018, 46, W451. 29757429 PMC6030990
  10. [10]H. Chen, A. Bian, L. F. Yang, X. Yin, J. Wang, C. Ti, Y. Miao, S. Peng, S. Xu, M. Liu, W. W. Qiu, Z. Yi, Oncogene 2021, 40, 1440. 33420372 PMC7906907
  11. [11]K. Siddiquee, S. Zhang, W. C. Guida, M. A. Blaskovich, B. Greedy, H. R. Lawrence, M. L. Yip, R. Jove, M. M. McLaughlin, N. J. Lawrence, S. M. Sebti, J. Turkson, Proc. Natl. Acad. Sci. USA 2007, 104, 7391. 17463090 PMC1863497
  12. [12]W. Zhao, S. Jaganathan, J. Turkson, J. Biol. Chem. 2010, 285, 35855. 20807764 PMC2975209
  13. [13]R. Jaber Chehayeb, T. J. Boggon, Front. Endocrinol. (Lausanne) 2020, 11, 575220. 33042028 PMC7530234
  14. [14]T. K. Sawyer, Biopolymers 1998, 47, 243. 9817027
  15. [15]M. J. Wagner, M. M. Stacey, B. A. Liu, T. Pawson, Cold Spring Harb. Perspect. Biol. 2013, 5, a008987. 24296166 PMC3839611
  16. [16]D. Takagi, Y. Tatsumi, T. Yokochi, A. Takatori, M. Ohira, T. Kamijo, S. Kondo, Y. Fujii, A. Nakagawara, Cancer Sci. 2013, 104, 563. 23360421 PMC7657181
  17. [17]C. K. Lindholm, J. D. Frantz, S. E. Shoelson, M. Welsh, Biochem. Biophys. Res. Commun. 2000, 278, 537. 11095946
  18. [18]M. Van Stry, A. Kazlauskas, S. L. Schreiber, K. Symes, Proc. Natl. Acad. Sci. USA 2005, 102, 8233. 15919820 PMC1149433
  19. [19]J. Jiao, R. Zhang, Z. Li, Y. Yin, X. Fang, X. Ding, Y. Cai, S. Yang, H. Mu, D. Zong, Y. Chen, Y. Zhang, J. Zou, J. Shao, Z. Huang, Nat. Commun. 2018, 9, 2504. 29950561 PMC6021382
  20. [20]G. M. Delgoffe, D. A. Vignali, JAKSTAT 2013, 2, e23060. 24058793 PMC3670269
  21. [21]R. Wang, P. Cherukuri, J. Luo, J. Biol. Chem. 2005, 280, 11528. 15649887
  22. [22]M. Zhao, Y. Tan, Q. Peng, C. Huang, Y. Guo, G. Liang, B. Zhu, Y. Huang, A. Liu, Z. Wang, M. Li, X. Gao, R. Wu, H. Wu, H. Long, Q. Lu, Nat. Commun. 2018, 9, 583. 29422534 PMC5805701
  23. [23]Y. Belo, Z. Mielko, H. Nudelman, A. Afek, O. Ben‐David, A. Shahar, R. Zarivach, R. Gordan, E. Arbely, Biochim. Biophys. Acta Gen. Subj. 2019, 1863, 1343. 31170499 PMC6625855
  24. [24]H. Lee, P. Zhang, A. Herrmann, C. Yang, H. Xin, Z. Wang, D. S. Hoon, S. J. Forman, R. Jove, A. D. Riggs, H. Yu, Proc. Natl. Acad. Sci. USA 2012, 109, 7765. 22547799 PMC3356652
  25. [25]Q. Zhang, H. Y. Wang, M. Marzec, P. N. Raghunath, T. Nagasawa, M. A. Wasik, Proc. Natl. Acad. Sci. USA 2005, 102, 6948. 15870198 PMC1100783
  26. [26]W. Y. Huang, S. D. Hsu, H. Y. Huang, Y. M. Sun, C. H. Chou, S. L. Weng, H. D. Huang, Nucleic Acids Res. 2015, 43, D856. 25398901 PMC4383953
  27. [27]J. Dong, X. D. Cheng, W. D. Zhang, J. J. Qin, J. Med. Chem. 2021, 64, 8884. 34170703
  28. [28]H. Lee, A. J. Jeong, S. K. Ye, BMB Rep. 2019, 52, 415. 31186087 PMC6675244
  29. [29]S. Zou, Q. Tong, B. Liu, W. Huang, Y. Tian, X. Fu, Mol. Cancer 2020, 19, 145. 32972405 PMC7513516
  30. [30]J. Braunstein, S. Brutsaert, R. Olson, C. Schindler, J. Biol. Chem. 2003, 278, 34133. 12832402
  31. [31]J. Yang, M. Chatterjee‐Kishore, S. M. Staugaitis, H. Nguyen, K. Schlessinger, D. E. Levy, G. R. Stark, Cancer Res. 2005, 65, 939. 15705894
  32. [32]J. Yang, X. Liao, M. K. Agarwal, L. Barnes, P. E. Auron, G. R. Stark, Genes Dev. 2007, 21, 1396. 17510282 PMC1877751
  33. [33]M. Dasgupta, H. Unal, B. Willard, J. Yang, S. S. Karnik, G. R. Stark, J. Biol. Chem. 2014, 289, 30763. 25217633 PMC4215253
  34. [34]H. Yue, W. Li, R. Desnoyer, S. S. Karnik, Cardiovasc. Res. 2010, 85, 90. 19696070 PMC2791056
  35. [35]P. Dutta, L. Zhang, H. Zhang, Q. Peng, P. R. Montgrain, Y. Wang, Y. Song, J. Li, W. X. Li, BMC Cancer 2020, 20, 145. 32087696 PMC7036253
  36. [36]J. Pencik, M. Schlederer, W. Gruber, C. Unger, S. M. Walker, A. Chalaris, I. J. Marie, M. R. Hassler, T. Javaheri, O. Aksoy, J. K. Blayney, N. Prutsch, A. Skucha, M. Herac, O. H. Kramer, P. Mazal, F. Grebien, G. Egger, V. Poli, W. Mikulits, R. Eferl, H. Esterbauer, R. Kennedy, F. Fend, M. Scharpf, M. Braun, S. Perner, D. E. Levy, T. Malcolm, S. D. Turner, et al., Nat. Commun. 2015, 6, 7736. 26198641 PMC4525303
  37. [37]H. Kojima, T. Inoue, H. Kunimoto, K. Nakajima, JAKSTAT 2013, 2, e25763. 24416650 PMC3876432
  38. [38]S. Zhuang, Cell Signal 2013, 25, 1924. 23707527 PMC4550442
  39. [39]M. Furqan, A. Akinleye, N. Mukhi, V. Mittal, Y. Chen, D. Liu, J. Hematol. Oncol. 2013, 6, 90. 24308725 PMC4029528
  40. [40]Y. Verhoeven, S. Tilborghs, J. Jacobs, J. De Waele, D. Quatannens, C. Deben, H. Prenen, P. Pauwels, X. B. Trinh, A. Wouters, E. L. J. Smits, F. Lardon, P. A. van Dam, Semin. Cancer Biol. 2020, 60, 41. 31605750
  41. [41]H. H. Ho, L. B. Ivashkiv, J. Biol. Chem. 2006, 281, 14111. 16571725
  42. [42]H. W. Lo, S. C. Hsu, M. Ali‐Seyed, M. Gunduz, W. Xia, Y. Wei, G. Bartholomeusz, J. Y. Shih, M. C. Hung, Cancer Cell 2005, 7, 575. 15950906
  43. [43]M. A. S. Abourehab, A. M. Alqahtani, B. G. M. Youssif, A. M. Gouda, Molecules 2021, 26, 6677. 34771085 PMC8587155
  44. [44]M. Asp, S. Giacomello, L. Larsson, C. Wu, D. Furth, X. Qian, E. Wardell, J. Custodio, J. Reimegard, F. Salmen, C. Osterholm, P. L. Stahl, E. Sundstrom, E. Akesson, O. Bergmann, M. Bienko, A. Mansson‐Broberg, M. Nilsson, C. Sylven, J. Lundeberg, Cell 2019, 179, 1647. 31835037
  45. [45]Q. Wang, P. H. Lu, Z. F. Shi, Y. J. Xu, J. Xiang, Y. X. Wang, L. X. Deng, P. Xie, Y. Yin, B. Zhang, H. J. Mu, W. Z. Qiao, H. Cui, J. Zou, Mol. Neurobiol. 2015, 52, 1106. 25301232
  46. [46]H. Y. Wu, E. Hudry, T. Hashimoto, K. Uemura, Z. Y. Fan, O. Berezovska, C. L. Grosskreutz, B. J. Bacskai, B. T. Hyman, J. Neurosci. 2012, 32, 5298. 22496575 PMC3354533
  47. [47]D. R. Croucher, M. Iconomou, J. F. Hastings, S. P. Kennedy, J. Z. Han, R. F. Shearer, J. McKenna, A. Wan, J. Lau, S. Aparicio, D. N. Saunders, Sci. Signal 2016, 9, 69. 27405979

Cited by

Sorted by citations

Authors
Wang, J., Huang, Z., Ji, L., Chen, C., Wan, Q., Xin, Y., Pu, Z., Li, K., Jiao, J., Yin, Y., Hu, Y., Gong, L., Zhang, R., Yang, X., Fang, X., Wang, M., Zhang, B., Shao, J., & Zou, J.
Affiliations
  • Wuxi People's Hospital (CN)
  • Department of Laboratory Medicine Wuxi People's Hospital of Nanjing Medical University Wuxi Jiangsu 214023 China
  • Nanjing Medical University (CN)
  • Jiangnan University (CN)
Corresponding author
  • Zhang, Bo
  • Shao, Junfei
  • Zou, Jian
ORCID
Venue
Advanced Science
Publisher
Wiley
Published
2022-07-17
Volume
9
Issue
26
Pages
e2200169-e2200169
ISSN
2198-3844 (ISSN-L)
DOI
10.1002/advs.202200169
PMC
PMC9475553
OpenAlex
W4285731533
Cited by
22
References
2
Citations by year
2026: 4 · 2025: 9 · 2024: 4 · 2023: 4 · 2022: 1
FWCI
1.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Advanced Science (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (81872056, 82172954, 81572468, 81372710, 81903391, 81802493, 82003581, 82172955)
  • Natural Science Foundation of Jiangsu Province (BK20191140, BK20190148)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords
STAT3, glioblastoma, tumor suppressor, STAT3 dimerization, STAT3 acetylation, DNMT1, DNA methylation, SH2 domain, STAT3 inhibitor, chemoresistance
MeSH terms
Glioblastoma, Humans, Phosphorylation, Genes, Tumor Suppressor, Dimerization, Intracellular Signaling Peptides and Proteins, STAT3 Transcription Factor, Protein Multimerization

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