Proteomic Analysis Reveals Aberrant O-GlcNAcylation of Extracellular Proteins from Breast Cancer Cell Secretion

Pukkavadee Netsirisawan1, Daranee Chokchaichamnankit2, Chantragan Srisomsap3

  • 1Applied Biological Sciences Program, Chulabhorn Graduate Institute, Laksi, Bangkok, Thailand.

Abstract

Insights

Aberrant O-GlcNAcylation was found in secreted proteins from breast cancer cells. This study identified specific O-GlcNAc-modified proteins, like HSP70 and TER ATPase, in cancer cell secretions, suggesting potential breast cancer biomarkers.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • O-GlcNAcylation is a key intracellular protein modification.
  • Aberrant O-GlcNAcylation is observed in breast cancer tissues.
  • Extracellular O-GlcNAc-modified proteins are poorly understood.

Purpose of the Study:

  • To investigate aberrant secretion of O-GlcNAc-modified proteins from breast cancer cells.
  • To identify specific extracellular O-GlcNAc-modified proteins in breast cancer.
  • To explore potential biomarkers for breast cancer detection.

Main Methods:

  • Preparation of intracellular and extracellular proteins from breast cancer and normal cells.
  • Examination of O-GlcNAcylation levels using immunoblotting.
  • Identification of O-GlcNAc-modified proteins via 2D gel electrophoresis and LC-MS/MS.

Main Results:

  • Significantly increased extracellular O-GlcNAcylation in breast cancer cells compared to normal cells.
  • Distinct O-GlcNAc patterns between intracellular and extracellular proteins.
  • Identification of increased O-GlcNAc-modified transitional endoplasmic reticulum ATPase (TER ATPase) and heat-shock 70 kDa (HSP70) in cancer cell secretions.

Conclusions:

  • Extracellular O-GlcNAcomic studies reveal aberrant secretion of O-GlcNAc-modified proteins in breast cancer.
  • O-GlcNAc-modified HSP70 and TER ATPase are elevated in breast cancer cell secretions.
  • These findings suggest potential utility of extracellular O-GlcNAc-modified proteins as breast cancer biomarkers.

Related Concept Videos

Proteoglycans01:05

Proteoglycans

Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
5.2K
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...
5.4K
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
4.6K
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...
5.1K
Matrix Proteoglycans and Glycoproteins01:21

Matrix Proteoglycans and Glycoproteins

Proteoglycans are extensively glycosylated proteins, commonly found in the extracellular matrix, interwoven with collagen fibers. Hyaline cartilage, the most common type of cartilage in the body, consists of short and dispersed collagen fibers associated with large amounts of proteoglycans. These proteoglycans have long negative charges that attract cations, which in turn attract water molecules. This influx of ions and water molecules swells up the proteoglycan like a water-soaked gel that can...
5.6K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.4K