Mesothelin overexpression promotes autocrine IL-6/sIL-6R trans-signaling to stimulate pancreatic cancer cell proliferation
Open accessAbstract
Mesothelin (MSLN) overexpression in pancreatic cancer (PC) leads to enhanced cell survival/proliferation and tumor progression. After screening for a number of growth factors/cytokines, we found that the MSLN expression correlated closely with interleukin (IL)-6 in human PC specimens and cell lines. Stably overexpressing MSLN in different PC cell lines (MIA-MSLN and Panc1-MSLN) led to higher IL-6 production. Silencing MSLN by small interfering RNA (siRNA) significantly reduced IL-6 levels. Blocking the observed constitutive activation of nuclear factor-kappaB (NF-κB) with IKK inhibitor wedelolactone in MIA-MSLN cells also reduced IL-6. Silencing IL-6 by siRNA reduced cell proliferation, cell cycle progression and induced apoptosis with significant decrease of c-myc/bcl-2. Interestingly, recombinant IL-6-induced proliferation of MIA-MSLN cells but not MIA-V cells. Although messenger RNA/protein levels of IL-6R did not vary, soluble IL-6R (sIL-6R) was significantly elevated in MIA-MSLN and was reduced by treatment with the TACE/ADAM17 inhibitor TAPI-1, indicating intramembrane IL-6R cleavage and IL-6 trans-signaling may be operative in MIA-MSLN cells. Blocking the IL-6/sIL-6R axis using sIL-6R antibody abrogated basal proliferation/survival as well as recombinant human IL-6-induced cell proliferation. Our data suggest that MSLN-activated NF-κB induces elevated IL-6 expression, which acts as a growth factor to support PC cell survival/proliferation through a novel auto/paracrine…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
MSLN promotes pancreatic cancer cell proliferation through autocrine IL-6 trans-signaling.
“MSLN also promotes pancreatic cancer cell proliferation through autocrine IL-6 trans-signaling (320).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [320]
Cites
Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
Kuilman, T., Michaloglou, C., Vredeveld, L. C. W., Douma, S., van Doorn, R., Desmet, C. J., Aarden, L. A., Mooi, W. J., & Peeper, D. S. (2008) · Cell · doi:10.1016/j.cell.2008.03.039 · Cited by 2,086 · see citing works
The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer
Naugler, W. E., & Karin, M. (2008) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.12.007 · Cited by 730 · see citing works
Yeh, H.-H., Lai, W.-W., Chen, H. H. W., Liu, H.-S., & Su, W.-C. (2006) · Oncogene · doi:10.1038/sj.onc.1209464 · Cited by 230 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453 · see citing works
“MSLN also promotes pancreatic cancer cell proliferation through autocrine IL-6 trans-signaling (320).”
BackgroundBharadwaj, U., Marin-Muller, C., Li, M., Chen, C., & Yao, Q. (2011) · Molecular Cancer · doi:10.1186/1476-4598-10-106 · Cited by 151 · see citing works
“MIAMSLN) express increased IL-6 at both mRNA/protein levels [31].”
BackgroundInfluentialSelf-citation
- Authors
- Bharadwaj, U., Marin-Muller, C., Li, M., Chen, C., & Yao, Q.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Yao, Q.
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-04-23
- Volume
- 32
- Issue
- 7
- Pages
- 1013-1024
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- PMC
- PMC3128561
- OpenAlex
- W2154363908
- Cited by
- 118
- References
- 3
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 14 · 2023: 7 · 2022: 9 · 2021: 4 · 2020: 12 · 2019: 7 · 2018: 6 · 2017: 7 · 2016: 6 · 2015: 4 · 2014: 9 · 2013: 4 · 2012: 8
- FWCI
- 3.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Carcinogenesis (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA140828, R21CA140828)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- mesothelin, pancreatic cancer, interleukin-6, soluble IL-6 receptor, autocrine signaling, NF-κB activation, cell proliferation, cell survival, apoptosis, c-Myc, Bcl-2, ADAM17, transarterial chemoembolization, anchorage-independent growth, combination therapy
- MeSH terms
- Mesothelin, Base Sequence, Cell Survival, Humans, Pancreatic Neoplasms, Blotting, Western, Signal Transduction, Interleukin-6, NF-kappa B, DNA Primers, Receptors, Interleukin-6, Cell Line, Tumor, Cell Proliferation, GPI-Linked Proteins
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
