Highlighted STAT3 As a Potential Drug Target for Cancer Therapy

Overview

Journal BMB Rep

Specialties Biochemistry
Molecular Biology

Date 2019 Jun 13

PMID 31186087

Citations 147

Authors

Haeri Lee

Ae Jin Jeong

Sang-Kyu Ye

Affiliations

Soon will be listed here.

Abstract

Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that regulates cell proliferation, differentiation, apoptosis, angiogenesis, inflammation and immune responses. Aberrant STAT3 activation triggers tumor progression through oncogenic gene expression in numerous human cancers, leading to promote tumor malignancy. On the contrary, STAT3 activation in immune cells cause elevation of immunosuppressive factors. Accumulating evidence suggests that the tumor microenvironment closely interacts with the STAT3 signaling pathway. So, targeting STAT3 may improve tumor progression, and anti-cancer immune response. In this review, we summarized the role of STAT3 in cancer and the tumor microenvironment, and present inhibitors of STAT3 signaling cascades. [BMB Reports 2019; 52(7): 415-423].

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References

Landowski T, Oshiro M, Turkson J, Levitzki A, Savino R, Ciliberto G . Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity. 1999; 10(1):105-15. DOI: 10.1016/s1074-7613(00)80011-4. View

Sano S, Itami S, Takeda K, Tarutani M, Yamaguchi Y, Miura H . Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis. EMBO J. 1999; 18(17):4657-68. PMC: 1171539. DOI: 10.1093/emboj/18.17.4657. View

Bromberg J, Darnell Jr J . The role of STATs in transcriptional control and their impact on cellular function. Oncogene. 2000; 19(21):2468-73. DOI: 10.1038/sj.onc.1203476. View

Epling-Burnette P, Liu J, Turkson J, Oshiro M, Kothapalli R, Li Y . Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression. J Clin Invest. 2001; 107(3):351-62. PMC: 199188. DOI: 10.1172/JCI9940. View

Turkson J, Ryan D, Kim J, Zhang Y, Chen Z, Haura E . Phosphotyrosyl peptides block Stat3-mediated DNA binding activity, gene regulation, and cell transformation. J Biol Chem. 2001; 276(48):45443-55. DOI: 10.1074/jbc.M107527200. View

Horiguchi A, Oya M, Marumo K, Murai M . STAT3, but not ERKs, mediates the IL-6-induced proliferation of renal cancer cells, ACHN and 769P. Kidney Int. 2002; 61(3):926-38. DOI: 10.1046/j.1523-1755.2002.00206.x. View

Schaefer L, Ren Z, Fuller G, Schaefer T . Constitutive activation of Stat3alpha in brain tumors: localization to tumor endothelial cells and activation by the endothelial tyrosine kinase receptor (VEGFR-2). Oncogene. 2002; 21(13):2058-65. DOI: 10.1038/sj.onc.1205263. View

Alas S, Bonavida B . Inhibition of constitutive STAT3 activity sensitizes resistant non-Hodgkin's lymphoma and multiple myeloma to chemotherapeutic drug-mediated apoptosis. Clin Cancer Res. 2003; 9(1):316-26. View

Wei D, Le X, Zheng L, Wang L, Frey J, Gao A . Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis. Oncogene. 2003; 22(3):319-29. DOI: 10.1038/sj.onc.1206122. View

10.

Kanai M, Konda Y, Nakajima T, Izumi Y, Kanda N, Nanakin A . Differentiation-inducing factor-1 (DIF-1) inhibits STAT3 activity involved in gastric cancer cell proliferation via MEK-ERK-dependent pathway. Oncogene. 2003; 22(4):548-54. DOI: 10.1038/sj.onc.1206109. View

11.

Kalluri R . Basement membranes: structure, assembly and role in tumour angiogenesis. Nat Rev Cancer. 2003; 3(6):422-33. DOI: 10.1038/nrc1094. View

12.

Buerger C, Nagel-Wolfrum K, Kunz C, Wittig I, Butz K, Hoppe-Seyler F . Sequence-specific peptide aptamers, interacting with the intracellular domain of the epidermal growth factor receptor, interfere with Stat3 activation and inhibit the growth of tumor cells. J Biol Chem. 2003; 278(39):37610-21. DOI: 10.1074/jbc.M301629200. View

13.

Wang T, Niu G, Kortylewski M, Burdelya L, Shain K, Zhang S . Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med. 2004; 10(1):48-54. DOI: 10.1038/nm976. View

14.

Yu H, Jove R . The STATs of cancer--new molecular targets come of age. Nat Rev Cancer. 2004; 4(2):97-105. DOI: 10.1038/nrc1275. View

15.

Herbeuval J, Lelievre E, Lambert C, Dy M, Genin C . Recruitment of STAT3 for production of IL-10 by colon carcinoma cells induced by macrophage-derived IL-6. J Immunol. 2004; 172(7):4630-6. DOI: 10.4049/jimmunol.172.7.4630. View

16.

Nagel-Wolfrum K, Buerger C, Wittig I, Butz K, Hoppe-Seyler F, Groner B . The interaction of specific peptide aptamers with the DNA binding domain and the dimerization domain of the transcription factor Stat3 inhibits transactivation and induces apoptosis in tumor cells. Mol Cancer Res. 2004; 2(3):170-82. View

17.

Silver D, Naora H, Liu J, Cheng W, Montell D . Activated signal transducer and activator of transcription (STAT) 3: localization in focal adhesions and function in ovarian cancer cell motility. Cancer Res. 2004; 64(10):3550-8. DOI: 10.1158/0008-5472.CAN-03-3959. View

18.

Dechow T, Pedranzini L, Leitch A, Leslie K, Gerald W, Linkov I . Requirement of matrix metalloproteinase-9 for the transformation of human mammary epithelial cells by Stat3-C. Proc Natl Acad Sci U S A. 2004; 101(29):10602-7. PMC: 489981. DOI: 10.1073/pnas.0404100101. View

19.

Saudemont A, Jouy N, Hetuin D, Quesnel B . NK cells that are activated by CXCL10 can kill dormant tumor cells that resist CTL-mediated lysis and can express B7-H1 that stimulates T cells. Blood. 2004; 105(6):2428-35. DOI: 10.1182/blood-2004-09-3458. View

20.

Turkson J, Zhang S, Palmer J, Kay H, Stanko J, Mora L . Inhibition of constitutive signal transducer and activator of transcription 3 activation by novel platinum complexes with potent antitumor activity. Mol Cancer Ther. 2005; 3(12):1533-42. View