Cited by 166Immune cells in cancerAngiogenesis and VEGF in CancerTGF-β signaling in diseases

PKN2 in colon cancer cells inhibits M2 phenotype polarization of tumor-associated macrophages via regulating DUSP6-Erk1/2 pathway

Open access
Cheng, Yang, Zhu, Yun, Xu, Jiajia, Yang, Min, Chen, Peiyu, Xu, Wanfu, Zhao, Junhong, Geng, Lanlan +1 more·2018·Molecular Cancer

Abstract

BACKGROUND: Protein kinase N2 (PKN2) is a PKC-related serine/threonine-protein kinase. PKN2 is required for tumor cell migration, invasion and apoptosis. However, the functional role of PKN2 in regulating tumor associated macrophages (TAMs) polarization in colon cancer has never been reported. METHODS: PKN2 expression in human colon cancer tissues was examined with immunohistochemistry (IHC). M1/M2 macrophage signatures were evaluated by RT-PCR, IHC and flow cytometry. The effects of PKN2 on tumor growth and TAM polarization were investigated both in vitro and in vivo. PKN2 targeted cytokines/pathway were analyzed by gene expression analysis and further confirmed by PCR, luciferase assay or western blot. Correlations between PKN2 and transcriptional factors for IL4 and IL10 were confirmed by ChIP-qPCR. The catalytic activities of PKN2 and DUSP6 were determined by kinase activity assay. Interactions between PKN2 and DUSP6 were confirmed by Co-IP. RESULTS: The expression of PKN2 in colon cancer cells predicted a favorable prognosis and was associated with low M2 macrophage content in human colon cancer tissues. PKN2 inhibited tumor growth in mice xenograft model and inhibited M2 phenotype polarization both in vitro and in vivo. Mechanistically, PKN2 suppresses the expression of IL4 and IL10 from colon cancer cells by inhibiting Erk1/2 phosphorylation, which is required for phosphorylation and binding of CREB and Elk-1 to the promoters of IL4 and IL10. DUSP6, which is phosphorylated and activated through direct association with PKN2, suppresses Erk1/2 activation. CONCLUSIONS: The expression of PKN2 in colon cancer cells suppresses tumor associated M2 macrophage polarization and tumor growth. Targeting PKN2 signaling pathway may provide a potential therapeutic strategy for colon cancer.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s12943-017-0747-z

Cites

54 of 54 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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?

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

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Cheng, Y., Zhu, Y., Xu, J., Yang, M., Chen, P., Xu, W., Zhao, J., Geng, L., & Gong, S.
Affiliations
  • Guangzhou Women and Children Medical Center (CN)
  • Nanfang Hospital (CN)
Corresponding author
Gong, Sitang
Venue
Molecular Cancer
Published
2018-01-24
Volume
17
Issue
1
Pages
13-13
ISSN
1476-4598 (ISSN-L)
OpenAlex
W2790033844
Cited by
161
References
54
Citations by year
2026: 11 · 2025: 22 · 2024: 25 · 2023: 22 · 2022: 28 · 2021: 37 · 2020: 8 · 2019: 7 · 2016: 1
FWCI
5.80
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Cancer (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 (81301758, 81602646)
  • Natural Science Foundation of Guangdong Province (2016A030310254)
  • China Postdoctoral Science Foundation (2016M600648)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
PKN2, colon cancer, tumor-associated macrophages, M2 macrophage polarization, DUSP6, ERK1/2 phosphorylation, IL-4, IL-10, CREB, Elk-1, tumor growth, prognostic factors, kinase signaling pathways
MeSH terms
Colonic Neoplasms, Humans, Immunohistochemistry, Macrophage Activation, Macrophages, Neoplasm Staging, Prognosis, Promoter Regions, Genetic, Protein Binding, Protein Kinase C, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Cytokines, MAP Kinase Signaling System, Cell Line, Tumor, ets-Domain Protein Elk-1, CREB-Binding Protein, Dual Specificity Phosphatase 6

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