Integrin-linked kinase expression in myeloid cells promotes colon tumorigenesis Article Swipe
Afsar U. Ahmed
,
Saleh Almasabi
,
Ron Firestein
,
Bryan Williams
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2023.1270194
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2023.1270194
Colorectal cancer (CRC) is one of the most common forms of cancer worldwide and treatment options for advanced CRC, which has a low 5-year survival rate, remain limited. Integrin-linked kinase (ILK), a multifunctional, scaffolding, pseudo-kinase regulating many integrin-mediated cellular processes, is highly expressed in many cancers. However, the role of ILK in cancer progression is yet to be fully understood. We have previously uncovered a pro-inflammatory role for myeloid-specific ILK in dextran sodium sulfate (DSS)-induced colitis. To establish a correlation between chronic intestinal inflammation and colorectal cancer (CRC), we investigated the role of myeloid-ILK in mouse models of CRC. When myeloid-ILK deficient mice along with the WT control mice were subjected to colitis-associated and APC min/+ -driven CRC, tumour burden was reduced by myeloid-ILK deficiency in both models. The tumour-promoting phenotype of macrophages, M2 polarization, in vitro was impaired by the ILK deficiency and the number of M2-specific marker CD206-expressing tumour-associated macrophages (TAMs) in vivo were significantly diminished in myeloid-ILK deficient mice. Myeloid-ILK deficient mice showed enhanced tumour infiltration of CD8+ T cells and reduced tumour infiltration of FOXP3+ T cells in colitis-associated and APC min/+ -driven CRC, respectively, with an overall elevated CD8+/FOXP3+ ratio suggesting an anti-tumour immune phenotypes. In patient CRC tissue microarrays we observed elevated ILK+ myeloid (ILK+ CD11b+) cells in tumour sections compared to adjacent normal tissues, suggesting a conserved role for myeloid-ILK in CRC development in both human and animal models. This study identifies myeloid-specific ILK expression as novel driver of CRC, which could be targeted as a potential therapeutic option for advanced disease.
Related Topics
Concepts
Integrin-linked kinase
Cancer research
Myeloid
Colorectal cancer
Carcinogenesis
Immunology
Medicine
Biology
Kinase
Cancer
Protein kinase A
Internal medicine
Cell biology
Cyclin-dependent kinase 2
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fimmu.2023.1270194
- OA Status
- gold
- Cited By
- 4
- References
- 81
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4388940255
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4388940255Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fimmu.2023.1270194Digital Object Identifier
- Title
-
Integrin-linked kinase expression in myeloid cells promotes colon tumorigenesisWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-11-21Full publication date if available
- Authors
-
Afsar U. Ahmed, Saleh Almasabi, Ron Firestein, Bryan WilliamsList of authors in order
- Landing page
-
https://doi.org/10.3389/fimmu.2023.1270194Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.3389/fimmu.2023.1270194Direct OA link when available
- Concepts
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Integrin-linked kinase, Cancer research, Myeloid, Colorectal cancer, Carcinogenesis, Immunology, Medicine, Biology, Kinase, Cancer, Protein kinase A, Internal medicine, Cell biology, Cyclin-dependent kinase 2Top concepts (fields/topics) attached by OpenAlex
- Cited by
-
4Total citation count in OpenAlex
- Citations by year (recent)
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2024: 4Per-year citation counts (last 5 years)
- References (count)
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81Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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