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p27 Expression in Wild-Type KRAS Colon Cancer

Marinović, Sonja ; Paladin, Iva ; Škrtić, Anita ; Ivković, Tina Catela LU ; Verbanac, Donatella and Kapitanović, Sanja (2026) In Journal of Cellular and Molecular Medicine 30(12).
Abstract

p27, a cyclin-dependent kinase inhibitor, functions as a tumour suppressor in the nucleus but may acquire oncogenic properties when mislocalized to the cytoplasm. While KRAS mutations can induce p27 phosphorylation and cytoplasmic retention, the regulation and significance of p27 expression in wild-type (WT) KRAS colorectal cancer (CRC) remain unclear. This study investigated the relationship between WT KRAS status and p27 localization, as well as the potential roles of miR-221/222 expression and the CDKN1B V109G polymorphism in CRC susceptibility. Immunohistochemical analysis of 50 WT KRAS CRCs and adjacent normal tissues revealed the highest percentage of p27-positive cells in the superficial layer of normal mucosa and significantly... (More)

p27, a cyclin-dependent kinase inhibitor, functions as a tumour suppressor in the nucleus but may acquire oncogenic properties when mislocalized to the cytoplasm. While KRAS mutations can induce p27 phosphorylation and cytoplasmic retention, the regulation and significance of p27 expression in wild-type (WT) KRAS colorectal cancer (CRC) remain unclear. This study investigated the relationship between WT KRAS status and p27 localization, as well as the potential roles of miR-221/222 expression and the CDKN1B V109G polymorphism in CRC susceptibility. Immunohistochemical analysis of 50 WT KRAS CRCs and adjacent normal tissues revealed the highest percentage of p27-positive cells in the superficial layer of normal mucosa and significantly fewer in the tumour center. WT KRAS tumours with KRAS expression showed increased p27 expression and predominant cytoplasmic localization at the invasive front, suggesting altered p27 subcellular distribution. miR-221/222 expression showed no correlation with p27 levels, and the CDKN1B V109G polymorphism was not associated with CRC risk. This study is the first to examine p27 localization in WT KRAS CRC. The observed association between WT KRAS expression and cytoplasmic p27 localization highlights a potential mechanism contributing to tumour progression through altered p27 function.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
colon adenocarcinoma, KRAS, miR-221/222, p27, V109G SNP
in
Journal of Cellular and Molecular Medicine
volume
30
issue
12
article number
e71248
publisher
Wiley-Blackwell
external identifiers
  • scopus:105042476635
  • pmid:42324979
ISSN
1582-1838
DOI
10.1111/jcmm.71248
language
English
LU publication?
yes
id
7235aec7-5b6d-420f-93e8-c29e63b7fe41
date added to LUP
2026-06-30 11:47:18
date last changed
2026-09-09 21:02:08
@article{7235aec7-5b6d-420f-93e8-c29e63b7fe41,
  abstract     = {{<p>p27, a cyclin-dependent kinase inhibitor, functions as a tumour suppressor in the nucleus but may acquire oncogenic properties when mislocalized to the cytoplasm. While KRAS mutations can induce p27 phosphorylation and cytoplasmic retention, the regulation and significance of p27 expression in wild-type (WT) KRAS colorectal cancer (CRC) remain unclear. This study investigated the relationship between WT KRAS status and p27 localization, as well as the potential roles of miR-221/222 expression and the CDKN1B V109G polymorphism in CRC susceptibility. Immunohistochemical analysis of 50 WT KRAS CRCs and adjacent normal tissues revealed the highest percentage of p27-positive cells in the superficial layer of normal mucosa and significantly fewer in the tumour center. WT KRAS tumours with KRAS expression showed increased p27 expression and predominant cytoplasmic localization at the invasive front, suggesting altered p27 subcellular distribution. miR-221/222 expression showed no correlation with p27 levels, and the CDKN1B V109G polymorphism was not associated with CRC risk. This study is the first to examine p27 localization in WT KRAS CRC. The observed association between WT KRAS expression and cytoplasmic p27 localization highlights a potential mechanism contributing to tumour progression through altered p27 function.</p>}},
  author       = {{Marinović, Sonja and Paladin, Iva and Škrtić, Anita and Ivković, Tina Catela and Verbanac, Donatella and Kapitanović, Sanja}},
  issn         = {{1582-1838}},
  keywords     = {{colon adenocarcinoma; KRAS; miR-221/222; p27; V109G SNP}},
  language     = {{eng}},
  number       = {{12}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Cellular and Molecular Medicine}},
  title        = {{p27 Expression in Wild-Type KRAS Colon Cancer}},
  url          = {{http://dx.doi.org/10.1111/jcmm.71248}},
  doi          = {{10.1111/jcmm.71248}},
  volume       = {{30}},
  year         = {{2026}},
}