Related Experiment Video

Updated: Oct 30, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

9.7K

Inhibition of YTHDF2 triggers proteotoxic cell death in MYC-driven breast cancer

Jaclyn M Einstein1, Mark Perelis1, Isaac A Chaim1

  • 1Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.

Molecular Cell
|July 3, 2021
PubMed

Insights

Researchers identified RNA-binding proteins (RBPs) that regulate MYC-driven cancers. Disrupting YTHDF2 protein function triggers cancer cell death, offering a potential therapeutic strategy for triple-negative breast cancer (TNBC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • RNA-binding proteins (RBPs) control gene expression after transcription.
  • Dysregulated RBP-RNA interactions are implicated in cancer development.
  • MYC-driven pathways are crucial in several cancer types.

Purpose of the Study:

  • To investigate the role of RBPs in cancer, particularly in MYC-driven oncogenesis.
  • To identify specific RBPs that could be targeted for cancer therapy.
  • To explore the function of YTHDF2 in triple-negative breast cancer (TNBC).

Main Methods:

  • Pooled CRISPR-Cas9 screening to identify functional RBPs in cancer.
  • eCLIP and m6A sequencing to map RBP-RNA interactions.
  • scRibo-STAMP profiling to analyze the translatome in single cells.

Main Results:

  • Identified 57 RBP candidates involved in MYC-driven pathways.
  • Disruption of YTHDF2 induced apoptosis in TNBC cells and tumors.
  • YTHDF2 targets mRNAs in the MAPK pathway, influencing epithelial-to-mesenchymal transition and translation.
  • YTHDF2 depletion caused specific translatome alterations linked to endoplasmic reticulum stress-induced apoptosis in TNBC.

Conclusions:

  • YTHDF2 plays a critical role in counteracting increased mRNA synthesis in MYC-driven breast cancers.
  • Targeting YTHDF2 represents a potential therapeutic strategy for TNBC.
  • RBPs are promising targets for cancer treatment by modulating gene expression regulation.
Keywords:
CRISPR screeningMYC-driven cancerN6-methyladenosineRNA-binding proteinSTAMPYTHDF2scRNA-seq

More Related Videos

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer04:20

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer

Published on: February 9, 2024

1.2K
Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

7.1K

Related Concept Videos

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...
4.8K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
7.2K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.1K
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...
4.0K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.0K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.7K