IFNγ induces Bcl3 expression by JAK1/STAT1/p65 signaling, resulting in increased IL‐8 expression in ovarian cancer cells
Open accessAbstract
We have recently shown that IFNγ, produced during cancer therapy, induces expression of the Bcl3 proto‐oncogene in ovarian cancer (OC) cells, resulting in their increased proliferation, migration, and invasion, but the mechanisms are unknown. Here, we demonstrate that the IFNγ‐induced Bcl3 expression is dependent on JAK1 and STAT1 signaling, and on p65 NFκB. Furthermore, the IFNγ‐induced Bcl3 expression is associated with an increased occupancy of Ser‐727 phosphorylated STAT1 and acetylated histone H3 at the Bcl3 promoter. Our data indicate that Bcl3 promotes expression of the pro‐inflammatory chemokine interleukin‐8 (IL‐8) in OC cells. These findings identify Bcl3 as a novel target of IFNγ/JAK1/STAT1 signaling and suggest that targeting the JAK1/STAT1 pathway may suppress IFNγ‐induced Bcl3 expression in OC.
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?
Pim3 and Bcl3 are direct transcriptional targets of the JAK-STAT pathway.
“two prominent rCap markers Pim3 and Bcl3 are direct transcriptional targets of the JAK-STAT pathway38,39”
From Endothelial Pim3 kinase protects the vascular barrier during lung metastasis (2024) · cites this paper as [38]
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
Mantovani, A., Allavena, P., Sica, A., & Balkwill, F. (2008) · Nature · doi:10.1038/nature07205 · Cited by 11,399 · see citing works
The Interleukin-8 Pathway in Cancer
Waugh, D. J. J., & Wilson, C. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4843 · Cited by 2,103 · see citing works
Interferons, immunity and cancer immunoediting
Dunn, G. P., Koebel, C. M., & Schreiber, R. D. (2006) · Nature Reviews Immunology · doi:10.1038/nri1961 · Cited by 1,617 · see citing works
The JAK-STAT Pathway at Twenty
Stark, G. R., & Darnell, J. E., Jr. (2012) · Immunity · doi:10.1016/j.immuni.2012.03.013 · Cited by 1,523 · see citing works
IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy
Ivashkiv, L. B. (2018) · Nature reviews. Immunology · doi:10.1038/s41577-018-0029-z · Cited by 1,374 · see citing works
Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion
Castro, F., Cardoso, A. P., Gonçalves, R. M., Serre, K., & Oliveira, M. J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00847 · Cited by 1,224 · see citing works
Antitumour actions of interferons: implications for cancer therapy
Parker, B. S., Rautela, J., & Hertzog, P. J. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.14 · Cited by 897 · see citing works
IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer
Abiko, K., Matsumura, N., Hamanishi, J., Horikawa, N., Murakami, R., Yamaguchi, K., Yoshioka, Y., Baba, T., Konishi, I., & Mandai, M. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.101 · Cited by 725 · see citing works
The CXCL8-CXCR1/2 pathways in cancer
Liu, Q., Li, A., Tian, Y., Wu, J. D., Liu, Y., Li, T., Chen, Y., Han, X., & Wu, K. (2016) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2016.08.002 · Cited by 666 · see citing works
Chemokines and chemokine receptors: new insights into cancer-related inflammation
Lazennec, G., & Richmond, A. J. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.01.003 · Cited by 651 · see citing works
Stat1-dependent and -independent pathways in IFN-γ-dependent signaling
Ramana, C. V., Gil, M. P., Schreiber, R. D., & Stark, G. R. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(01)02118-4 · Cited by 555 · see citing works
Schalper, K. A., Carleton, M. O., Zhou, M., Chen, T., Feng, Y., Huang, S., Walsh, A. M., Baxi, V. A., Pandya, D., Baradet, T. C., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0856-x · Cited by 550 · see citing works
Liakou, C. I., Kamat, A., Tang, D. N., Chen, H., Sun, J., Troncoso, P., Logothetis, C., & Sharma, P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806075105 · Cited by 549 · see citing works
Mutations in the NF-κB signaling pathway: implications for human disease
Courtois, G., & Gilmore, T. D. (2006) · Oncogene · doi:10.1038/sj.onc.1209939 · Cited by 525 · see citing works
Bours, V. (1993) · Cell · doi:10.1016/0092-8674(93)90401-b · Cited by 502 · see citing works
Radiation-Induced IFN-γ Production within the Tumor Microenvironment Influences Antitumor Immunity
Lugade, A. A., Sorensen, E. W., Gerber, S. A., Moran, J. P., Frelinger, J. G., & Lord, E. M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.5.3132 · Cited by 485 · see citing works
Sanmamed, M. F., Perez‐Gracia, J. L., Schalper, K. A., Fusco, J. P., González, Á., Rodriguez-Ruiz, M. E., Oñate, C., Perez, G., Alfaro, C., Martín‐Algarra, S., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx190 · Cited by 458 · see citing works
Cogswell, P. C., D, D. C. G., Funkhouser, W. K., & Baldwin, A. S. (2000) · Oncogene · doi:10.1038/sj.onc.1203412 · Cited by 452 · see citing works
PD-1 blockade enhances T-cell migration to tumors by elevating IFN-γ inducible chemokines
Peng, W., Liu, C., Xu, C., Lou, Y., Chen, J., Yang, Y., Yagita, H., Overwijk, W. W., Lizée, G., Radvanyi, L., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1187 · Cited by 432 · see citing works
Fujita, T., Nolan, G. P., Liou, H. C., Scott, M. L., & Baltimore, D. (1993) · Genes & Development · doi:10.1101/gad.7.7b.1354 · Cited by 409 · see citing works
Regulatory Networks Involving STATs, IRFs, and NFκB in Inflammation
Platanitis, E., & Decker, T. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02542 · Cited by 251 · see citing works
Candidate proto-oncogene bcl-3 encodes a subunit-specific inhibitor of transcription factor NF-κB
Wulczyn, F. G., Naumann, M., & Scheidereit, C. (1992) · Nature · doi:10.1038/358597a0 · Cited by 247 · see citing works
Nolan, G. P., Fujita, T., Bhatia, K. G., Huppi, C., Liou, H., Scott, M. L., & Baltimore, D. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.6.3557 · Cited by 237 · see citing works
Franzoso, G., Bours, V., Azarenko, V., Park, S., Tomita-Yamaguchi, M., KANNO, T., Brown, K., & Siebenlist, U. K. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06067.x · Cited by 171 · see citing works
Sun, L., Wang, Q., Chen, B., Zhao, Y., Shen, B., Wang, H., Xu, J., Zhu, M., Zhao, X., Xu, C., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0988-9 · Cited by 147 · see citing works
Alberts, D. S., Marth, C., Alvarez, R. D., Johnson, G. A., Bidziński, M., Kardatzke, D. R., Bradford, W. Z., Loutit, J. S., Kirn, D. H., Clouser, M. C., et al. (2008) · Gynecologic Oncology · doi:10.1016/j.ygyno.2008.01.005 · Cited by 127 · see citing works
Mathas, S., Jöhrens, K., Joos, S., Lietz, A., Hummel, F., Janz, M., Jundt, F., Anagnostopoulos, I., Bommert, K., Lichter, P., et al. (2005) · Blood · doi:10.1182/blood-2004-09-3620 · Cited by 122 · see citing works
IL-8 and cancer prognosis on immunotherapy
Bakouny, Z., & Choueiri, T. K. (2020) · Nature Medicine · doi:10.1038/s41591-020-0873-9 · Cited by 118 · see citing works
The proto-oncogene bcl-3 encodes an I kappa B protein.Preprint
Kerr, L. D., Duckett, C. S., Wamsley, P., Zhang, Q., Chiao, P. J., Nabel, G. J., McKeithan, T. W., Baeuerle, P. A., & Verma, I. M. (1992) · Genes & Development · doi:10.1101/gad.6.12a.2352 · Cited by 115 · see citing works
BCL3 Encodes a Nuclear Protein Which Can Alter the Subcellular Location of NF-κB Proteins
Zhang, Q., DiDonato, J. A., Karin, M., & McKeithan, T. W. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.6.3915-3926.1994 · Cited by 108 · see citing works
NF-κB-inducible BCL-3 Expression Is an Autoregulatory Loop Controlling Nuclear p50/NF-κB1 Residence
Brasier, A. R., Lu, M., Hai, T., Lu, Y. C., & Boldogh, I. R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102949200 · Cited by 96 · see citing works
Martín-Subero, J. I. (2006) · Blood · doi:10.1182/blood-2005-09-3843 · Cited by 90 · see citing works
Maldonado, V., & Meléndez-Zajgla, J. (2011) · Molecular Cancer · doi:10.1186/1476-4598-10-152 · Cited by 86 · see citing works
NF-ĸB and Bcl-3 Activation Are Prognostic in Metastatic Colorectal Cancer
Puvvada, S. D., Funkhouser, W. K., Greene, K. G., Deal, A. M., Chu, H., Baldwin, A. S., Tepper, J. E., & O’Neil, B. H. (2010) · Oncology · doi:10.1159/000313697 · Cited by 83 · see citing works
Brocke-Heidrich, K., Ge, B., Cvijic, H., Pfeifer, G., Löffler, D., Henze, C., McKeithan, T. W., & Horn, F. (2006) · Oncogene · doi:10.1038/sj.onc.1209711 · Cited by 83 · see citing works
Bcl3 Selectively Promotes Metastasis of ERBB2-Driven Mammary Tumors
Wakefield, A., Soukupová, J., Montagne, A., Ranger, J. J., French, R., Muller, W. J., & Clarkson, R. W. E. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1321 · Cited by 77 · see citing works
Nolan, G. P., Fujita, T., Bhatia, K. G., Huppi, C., Liou, H., Scott, M. L., & Baltimore, D. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.6.3557-3566.1993 · Cited by 69 · see citing works
Interleukin-9 Regulates NF-κB Activity Through BCL3 Gene Induction
Richard, M., Louahed, J., Demoulin, J., & Renauld, J. (1999) · Blood · doi:10.1182/blood.v93.12.4318 · Cited by 66 · see citing works
Marth, C., Windbichler, G. H., Hausmaninger, H., Petru, E., Estermann, K., Pelzer, A. E., & Mueller‐Holzner, E. (2006) · International Journal of Gynecological Cancer · doi:10.1111/j.1525-1438.2006.00622.x · Cited by 64 · see citing works
Piaszyk-Borychowska, A., Széles, L., Csermely, A., Chiang, H.-C., Wesoły, J., Lee, C., Nagy, L., & Bluyssen, H. A. R. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01253 · Cited by 63 · see citing works
Bcl3 regulates pro-survival and pro-inflammatory gene expression in cutaneous T-cell lymphoma
Chang, T., & Vancurova, I. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.07.012 · Cited by 58 · see citing works
Self-citationZou, Y., Uddin, M. M., Padmanabhan, S., Zhu, Y. B., Bu, P., Vančura, A., & Vancurova, I. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.004084 · Cited by 55 · see citing works
Self-citationElliott, S. F., Hays, E., Mayor, M. B., Sporn, M. B., & Vincenti, M. P. (2003) · Arthritis Research & Therapy · doi:10.1186/ar792 · Cited by 46 · see citing works
Roles of IKK-β, IRF1, and p65 in the Activation of Chemokine Genes by Interferon-γ
Shultz, D. B., Rani, M. R. S., Fuller, J. D., Ransohoff, R. M., & Stark, G. R. (2009) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2009.0034 · Cited by 43 · see citing works
NF-κB Regulates BCL3 Transcription in T Lymphocytes Through an Intronic Enhancer
Ge, B., Li, O., Wilder, P. J., Rizzino, A., & McKeithan, T. W. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.8.4210 · Cited by 39 · see citing works
BCL3 exerts an oncogenic function by regulating STAT3 in human cervical cancer
Zhao, H., Wang, W., Zhao, Q., Hu, G., Deng, K., & Liu, Y. (2016) · OncoTargets and Therapy · doi:10.2147/ott.s118184 · Cited by 38 · see citing works
Brenne, A., Fagerli, U., Shaughnessy, J. D., Våtsveen, T. K., Rø, T. B., Hella, H., Zhan, F., Barlogie, B., Sundan, A., Børset, M., et al. (2009) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2009.01225.x · Cited by 37 · see citing works
Wu, J., Li, L., Jiang, G., Zhan, H., & Wang, N. (2016) · International Journal of Oncology · doi:10.3892/ijo.2016.3729 · Cited by 34 · see citing works
Dai, L., Niu, J., & Feng, Y. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14701 · Cited by 25 · see citing works
Padmanabhan, S., Gaire, B., Zou, Y., Uddin, M. M., DeLeon, D., & Vancurova, I. (2021) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2021.106093 · Cited by 22 · see citing works
Self-citationThe Discovery of a Novel Antimetastatic Bcl3 Inhibitor
Soukupová, J., Bordoni, C., Turnham, D. J., Yang, W. W., Seaton, G., Gruca, A., French, R., Lee, K. Y., Varnava, A., Piggott, L., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0283 · Cited by 21 · see citing works
Shultz, D. B., Fuller, J. D., Yang, Y., Sizemore, N., Rani, M. R. S., & Stark, G. R. (2007) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2007.0031 · Cited by 18 · see citing works
IL6 and BCL3 Expression Are Potential Biomarkers in Esophageal Squamous Cell Carcinoma
Soares‐Lima, S. C., Gonzaga, I. M., Camuzi, D., Nicolau‐Neto, P., da Silva, R. V., Guaraldi, S., Ferreira, M. A. D. S., Hernández‐Vargas, H., Herceg, Z., & Pinto, L. F. R. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.722417 · Cited by 16 · see citing works
Analysis of IFNγ-Induced Migration of Ovarian Cancer Cells
Gaire, B., Uddin, M. M., Zou, Y., & Vancurova, I. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0247-8_8 · Cited by 7 · see citing works
Self-citationZou, Y., Padmanabhan, S., & Vancurova, I. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0247-8_20 · Cited by 4 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Multifaceted roles for BCL3 in cancer: a proto-oncogene comes of age
Seaton, G., Smith, H., Brancale, A., Westwell, A. D., & Clarkson, R. W. E. (2024) · Molecular Cancer · doi:10.1186/s12943-023-01922-8 · Cited by 32 · see citing works
IFNγ-Induced Bcl3, PD-L1 and IL-8 Signaling in Ovarian Cancer: Mechanisms and Clinical Significance
Reddy, S. P., Sadia, F. Z., Vančura, A., & Vancurova, I. (2024) · Cancers · doi:10.3390/cancers16152676 · Cited by 16 · see citing works
Self-citationReddy, S. P., Sham, R., Smith, K., Gaire, B., Vančura, A., & Vancurova, I. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.108339 · Cited by 12 · see citing works
Self-citationEndothelial Pim3 kinase protects the vascular barrier during lung metastasis
Santio, N. M., Ganesh, K., Kaipainen, P. P., Halme, A., Seyednasrollah, F., Arbash, E., Hänninen, S., Kivelä, R., Carpen, O., & Saharinen, P. (2024) · Nature Communications · doi:10.1038/s41467-024-54445-1 · Cited by 9 · see citing works
Kübelbeck, T., Wichmann, N. O., Raj, T., Raj, C., Ohnmacht, C., Hövelmeyer, N., Kramer, D., & Heissmeyer, V. (2025) · European Journal of Immunology · doi:10.1002/eji.202451273 · Cited by 8 · see citing works
Watrowski, R., Schuster, E., Hofstetter, G., Fischer, M. B., Mahner, S., Gorp, T. V., Polterauer, S., Zeillinger, R., & Obermayr, E. (2024) · Biomedicines · doi:10.3390/biomedicines12020321 · Cited by 8 · see citing works
Inflammatory milieu and role of epigenetic modifications in high-grade serous ovarian cancer
Pradhan, S., Kabekkodu, S. P., Eswaran, S., Kumar, N. A. N., Upadhya, D., Chakrabarty, S., & Devi, V. (2026) · Clinical Epigenetics · doi:10.1186/s13148-026-02080-6 · Cited by 3 · see citing works
Reddy, S. P., Zhu, Y. B., & Vancurova, I. (2026) · Methods in molecular biology · doi:10.1007/978-1-0716-4901-5_34 · Cited by 1 · see citing works
Self-citationSTAT1 and STAT3 signaling in ovarian cancer: prognostic biomarkers and therapeutic targets
Rodman, E. P. B., Bhagwate, A., Smith, H. M., Emch, M. J., Pearson, N. A., Sun, Z., & Hawse, J. R. (2026) · BMC Cancer · doi:10.1186/s12885-026-16226-5 · Cited by 1 · see citing works
Angelicola, S., Frascino, M., Chillico, I. C., Michel, P. L. S., Pistone, D., Semprini, M. S., Pittino, O. M., Ardizzoni, A., Alessio, N. L., Agustoni, F., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1945729
- Authors
- Gaire, B., Padmanabhan, S., Zou, Y., Uddin, M. M., Reddy, S. U., & Vancurova, I.
- Affiliations
- St. John's University (US)
- Department of Biological Sciences St. John's University New York NY USA
- Corresponding author
- Vancurova, Ivana
- Venue
- FEBS Open Bio
- Publisher
- Wiley
- Published
- 2023-07-18
- Volume
- 13
- Issue
- 8
- Pages
- 1495-1506
- ISSN
- 2211-5463 (ISSN-L)
- PMC
- PMC10392061
- OpenAlex
- W4375855629
- Cited by
- 10
- References
- 55
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 4
- FWCI
- 1.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- FEBS Open Bio (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Cancer Institute (CA202775)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- interferon-gamma, boron trichloride, ovarian cancer, JAK1/STAT1 signaling, NF-κB p65, interleukin-8, histone H3 acetylation, chemokine expression
- MeSH terms
- Female, Humans, Interferon-gamma, Ovarian Neoplasms, Signal Transduction, Interleukin-8, NF-kappa B, STAT1 Transcription Factor, Janus Kinase 1
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
