Related Experiment Video

Updated: Jun 4, 2025

Extraction of Extracellular Vesicles from Whole Tissue
09:03

Extraction of Extracellular Vesicles from Whole Tissue

Published on: February 7, 2019

14.9K

Biological functions of extracellular vesicle double C2-like domain beta in cervical cancer

Sangavi Eswaran1, Samatha Bhat1,2, Dinesh Upadhya3

  • 1Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.

Scientific Reports
|January 2, 2025
PubMed

Insights

Extracellular vesicles (EVs) transfer Double C-2 Like Domain Beta (DOC2B) to cervical cancer cells, inhibiting metastasis. Intracellular calcium influences DOC2B EV localization and tumor-suppressive activity, offering new therapeutic strategies.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Cervical cancer (CC) metastasis is a significant clinical challenge.
  • The tumor-suppressive protein Double C-2 Like Domain Beta (DOC2B) inhibits metastasis by inducing senescence and epithelial-mesenchymal transition (EMT) inhibition.
  • The role of extracellular vesicle (EV)-mediated DOC2B trafficking in CC remains uninvestigated.

Purpose of the Study:

  • To investigate the EV-mediated trafficking of DOC2B in cervical cancer.
  • To determine the impact of EV-delivered DOC2B on CC cell behavior and tumor suppressive activity.
  • To elucidate the role of intracellular calcium in DOC2B localization to EVs.

Main Methods:

  • Ectopic expression of DOC2B in SiHa cervical cancer cells.
  • Isolation and characterization of EVs from DOC2B-expressing and control cells.
  • Co-incubation of recipient cells (SiHa, HeLa) with DOC2B-expressing EVs.
  • Assessment of cellular changes, proliferation, migration, senescence, apoptosis, oxidative stress, and metabolite profiles.

Main Results:

  • DOC2B was successfully localized to EVs, with its transfer potentially dependent on intracellular calcium.
  • DOC2B-expressing EVs induced morphological changes, suppressed growth and migration, and promoted anoikis in recipient CC cells.
  • EV-mediated DOC2B transfer elevated reactive oxygen species (ROS) and calcium, promoted lipid accumulation, reduced AKT1/ERK1/2 signaling, enhanced senescence, and increased cisplatin sensitivity.

Conclusions:

  • EV-mediated transfer of DOC2B represents a novel mechanism for suppressing cervical cancer progression.
  • Intracellular calcium is crucial for DOC2B localization into EVs and its subsequent tumor-suppressive functions.
  • Targeting EV-mediated DOC2B delivery holds potential for CC therapeutic strategies.
Keywords:
CalciumCervical cancerDOC2BEMTExtracellular vesiclesSenescence

More Related Videos

In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells08:02

In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells

Published on: September 23, 2021

2.5K
An Enrichment Method for Small Extracellular Vesicles Derived from Liver Cancer Tissue10:33

An Enrichment Method for Small Extracellular Vesicles Derived from Liver Cancer Tissue

Published on: February 3, 2023

1.2K

Related Concept Videos

Overview of Secretory Vesicles01:33

Overview of Secretory Vesicles

Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
8.4K
Vesicular Tubular Clusters01:45

Vesicular Tubular Clusters

After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
2.4K
Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
3.4K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.3K
COP Coated Vesicles00:59

COP Coated Vesicles

Membrane-enclosed structures called vesicles transport proteins and lipids across the cell. The vesicles derive their cargo from the plasma membrane, Golgi, ER, or endosome. Coated vesicles are spherical, protein-coated carriers with a 50–100 nm diameter that mediate bidirectional transport between the ER and the Golgi. The distribution of proteins between the ER and Golgi complex is dynamic and is maintained by different coated vesicles. Their formation is driven by the assembly of...
7.7K