Phosphorylated 4E-BP1 is associated with tumor progression and adverse prognosis in colorectal cancer

Neoplasma
|June 9, 2017
PubMed

Insights

High levels of phosphorylated 4E-BP1 (p-4E-BP1) are linked to colorectal cancer progression. This protein may serve as a novel biomarker for predicting patient outcomes and survival in colorectal cancer (CRC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Phosphorylation of eukaryotic translation initiation factor 4E (eIF4E)-binding protein (4E-BP1) releases eIF4E, promoting cancer-associated protein synthesis.
  • Elevated p-4E-BP1 levels are implicated in various cancers, but its role in colorectal cancer (CRC) requires further elucidation.

Purpose of the Study:

  • To evaluate the expression of phosphorylated 4E-BP1 (p-4E-BP1) in colorectal cancer (CRC) tissues.
  • To investigate the correlation between p-4E-BP1 levels and clinicopathological factors in CRC patients.
  • To assess the prognostic value of p-4E-BP1 for patient survival in CRC.

Main Methods:

  • Immunohistochemistry and Western blot were employed to detect p-4E-BP1 levels in 164 CRC patients.
  • mRNA and protein expression of 4E-BP1 were compared between tumor and adjacent normal colorectal tissues.
  • Cox regression analysis was utilized to determine the prognostic significance of p-4E-BP1.

Main Results:

  • A high level of p-4E-BP1 was observed in 57.9% of CRC patients.
  • p-4E-BP1 levels significantly correlated with tumor differentiation, invasive depth, lymph node metastasis, and TNM stage.
  • While 4E-BP1 mRNA and protein levels did not differ, p-4E-BP1 was markedly increased in CRC tissues.

Conclusions:

  • Elevated p-4E-BP1 is associated with tumor progression and adverse prognosis in colorectal cancer.
  • p-4E-BP1 serves as an independent adverse prognostic factor for overall survival and progression-free survival in CRC.
  • p-4E-BP1 shows potential as a novel biomarker for predicting clinical outcomes in colorectal cancer patients.

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR 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...
4.9K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.9K
Abnormal Proliferation02:23

Abnormal 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...
5.3K
Tumor Progression02:07

Tumor 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...
7.6K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.3K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.4K