title: Differential expression of IL-17, 22 and 23 in the progression of colorectal cancer in patients with K-ras mutation: Ras signal inhibition and crosstalk with GM-CSF and IFN-γ.
abstract: Recent studies have suggested that aberrant K-ras signaling is responsible for triggering immunological responses and inflammation-driven tumorigenesis. Interleukins IL-17, IL-22, and IL-23 have been reported in various types of malignancies, but the exact mechanistic role of these molecules remains to be elucidated. Given the role of K-ras and the involvement of interleukins in colorectal tumorigenesis, research efforts are reported for the first time, showing that differentially expressed interleukin IL-17, IL-22, and IL-23 levels are associated with K-ras in a stage-specific fashion along colorectal cancer progression. Specifically, a) the effect of K-ras signaling was investigated in the overall expression of interleukins in patients with colorectal cancer and healthy controls, and b) an association was established between mutant K-ras and cytokines GM-CSF and IFN-γ. The results indicate that specific interleukins are differentially expressed in K-ras positive patients and the use of K-ras inhibitor Manumycin A decreases both interleukin levels and apoptosis in Caco-2 cells by inhibiting cell viability. Finally, inflammation-driven GM-CSF and IFN-γ levels are modulated through interleukin expression in tumor patients, with interleukin expression in the intestinal lumen and cancerous tissue mediated by aberrant K-ras signaling. Collectively, the findings a) indicate that interleukin expression is influenced by ras signaling and specific interleukins play an oncogenic promoter role in colorectal cancer, highlighting the molecular link between inflammation and tumorigenesis, and b) accentuate the interwoven molecular correlations as leads to new therapeutic approaches in the future.
authors.affiliation: Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Savvas
authors.initials: S
authors.lastname: Petanidis
authors.forename: Doxakis
authors.initials: D
authors.lastname: Anestakis
authors.forename: Maria
authors.initials: M
authors.lastname: Argyraki
authors.forename: Margarita
authors.initials: M
authors.lastname: Hadzopoulou-Cladaras
authors.forename: Athanasios
authors.initials: A
authors.lastname: Salifoglou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D020869:Gene Expression Profiling; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics* / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics* / Q000378:metabolism; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011090:Polyenes / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D018631:ras Proteins / Q000235:genetics*; D000097043:Interleukin-22
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D011090:Polyenes; D053284:Polyunsaturated Alkamides; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000097043:Interleukin-22; C117307:KRAS protein, human; C054474:manumycin
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