Related Experiment Video
Updated: Jun 23, 2026
10:13
A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells
Published on: July 3, 2013
p27 Expression in Wild-Type KRAS Colon Cancer.
Sonja Marinović1, Iva Paladin2, Anita Škrtić3
1Division of Molecular Medicine, Ruđer Bosković Institute, Zagreb, Croatia.
Journal of Cellular and Molecular Medicine
|June 22, 2026
Summary
In wild-type KRAS colorectal cancer (CRC), p27 (a cell cycle regulator) shifts to the cytoplasm, potentially driving tumor growth. This cytoplasmic shift, linked to WT KRAS expression, suggests a new therapeutic target for CRC progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- P27 (a cyclin-dependent kinase inhibitor) acts as a tumor suppressor in the nucleus but can promote cancer when in the cytoplasm.
- KRAS mutations cause p27 to move to the cytoplasm, but its role in wild-type (WT) KRAS colorectal cancer (CRC) is unknown.
Purpose of the Study:
- To investigate p27 localization in WT KRAS CRC.
- To explore the roles of miR-221/222 and the CDKN1B V109G polymorphism in CRC risk.
Main Methods:
- Immunohistochemistry was used to analyze p27 expression and localization in 50 WT KRAS CRC tissues and adjacent normal tissues.
- Correlations between p27 levels, WT KRAS expression, miR-221/222 expression, and the CDKN1B V109G polymorphism were assessed.
Main Results:
- P27 was most abundant in the superficial layer of normal mucosa, with significantly lower levels in tumor centers.
- WT KRAS tumors expressing KRAS showed increased p27 levels and predominantly cytoplasmic localization at the invasive front.
- miR-221/222 expression and the CDKN1B V109G polymorphism were not associated with CRC risk or p27 levels.
Conclusions:
- This study is the first to examine p27 localization in WT KRAS CRC.
- WT KRAS expression is associated with cytoplasmic p27 localization, suggesting a mechanism for tumor progression via altered p27 function.
Related Concept Videos
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
02:07Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
01:24Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...