Related Experiment Video

Updated: Feb 23, 2026

Author Spotlight: Impact of Intergenic Interactions on Disease-Identifying Dark Biomarkers
03:37

Author Spotlight: Impact of Intergenic Interactions on Disease-Identifying Dark Biomarkers

Published on: March 1, 2024

1.4K

Splice variants of cytosolic polyadenylation element-binding protein 2 (CPEB2) differentially regulate pathways

James T DeLigio1, Grace Lin1, Charles E Chalfant2,3,4,5,6,7,8,9

  • 1From the Department of Biochemistry and Molecular Biology and.

The Journal of Biological Chemistry
|September 15, 2017
PubMed

Insights

Alternative splicing of cytosolic polyadenylation element-binding protein 2 (CPEB2) generates isoforms that drive breast cancer metastasis. CPEB2B isoform activates pathways promoting anoikis resistance and epithelial-to-mesenchymal transition, crucial for cancer spread.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Cytosolic polyadenylation element-binding protein 2 (CPEB2) has two isoforms, CPEB2A and CPEB2B, generated by alternative RNA splicing.
  • CPEB2B is overexpressed in aggressive breast cancers, while CPEB2A is lost.
  • This isoform switch is linked to anoikis resistance and metastasis in breast cancer cells.

Purpose of the Study:

  • To investigate the molecular mechanisms by which CPEB2 isoforms influence cancer-related phenotypes.
  • To elucidate how CPEB2 alternative splicing regulates pathways involved in metastasis and anoikis resistance.

Main Methods:

  • Next-generation sequencing was performed on triple-negative breast cancer cells with specifically downregulated CPEB2 isoforms.
  • Analysis focused on epithelial-to-mesenchymal transition and hypoxic response pathways.
  • Expression levels of key transcription factors, including HIF1α and TWIST1, were examined.

Main Results:

  • Downregulation of CPEB2B, but not CPEB2A, inhibited pathways driving epithelial-to-mesenchymal transition and hypoxic response.
  • CPEB2B was found to induce the expression of transcription factors HIF1α and TWIST1.
  • CPEB2B acts as a translational activator for TWIST1 and HIF1α, which are essential for anoikis resistance and metastasis.

Conclusions:

  • CPEB2 alternative splicing is a critical regulator of cellular pathways associated with cancer progression.
  • The CPEB2B isoform promotes breast cancer metastasis and anoikis resistance by activating HIF1α and TWIST1.
  • Targeting CPEB2 splicing may offer a therapeutic strategy for aggressive breast cancers.
Keywords:
CPEB2alternative splicingbreast cancercytoplasmic polyadenylationepithelial-mesenchymal transition (EMT)epithelial-to-mesenchymal transitionhypoxia-inducible factor (HIF)hypoxic responsemRNA

More Related Videos

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients12:13

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

Published on: November 19, 2019

7.3K
Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

9.5K

Related Concept Videos

RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
60.8K
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
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
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
6.7K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
9.8K
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