Related Experiment Video

Updated: Jun 17, 2025

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

7.2K

tRF-27 competitively Binds to G3BPs and Activates MTORC1 to Enhance HER2 Positive Breast Cancer Trastuzumab Tolerance

Yaozhou He1, Yincheng Liu1, Jue Gong1

  • 1Department of Oncology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, China.

International Journal of Biological Sciences
|August 8, 2024
PubMed

Insights

Trna-derived fragment 27 (tRF-27) promotes trastuzumab resistance in HER2-positive breast cancer by interacting with G3BPs. This interaction enhances cell proliferation and treatment tolerance, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • HER2-positive breast cancer affects approximately 20% of patients.
  • Trastuzumab resistance limits treatment efficacy in HER2-positive breast cancer.
  • Trna-derived fragments (tRFs) are emerging regulators in cancer biology.

Purpose of the Study:

  • To investigate the role of tRF-27 in trastuzumab resistance in HER2-positive breast cancer.
  • To identify the molecular mechanisms by which tRF-27 influences trastuzumab sensitivity.

Main Methods:

  • Expression analysis of tRF-27 in trastuzumab-resistant cells.
  • RNA-pulldown, mass spectrometry, RNA-immunoprecipitation (RIP), and co-immunoprecipitation (co-IP) assays.
  • Investigation of tRF-27 binding to G3BPs and its impact on cellular pathways.

Main Results:

  • tRF-27 expression is elevated in trastuzumab-resistant cells and predicts resistance.
  • tRF-27 directly binds to the NTF2 domain of G3BPs.
  • tRF-27 promotes cell proliferation and trastuzumab tolerance by inhibiting G3BPs/TSC/MTORC1 pathway.

Conclusions:

  • tRF-27 is a key regulator of trastuzumab resistance in HER2-positive breast cancer.
  • The tRF-27/G3BPs interaction offers a novel therapeutic target to overcome trastuzumab resistance.
Keywords:
G3BPsHER2-positive breast cancerMTORC1Trastuzumab resistancetRNA-derived fragment

More Related Videos

Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery13:19

Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery

Published on: April 26, 2024

2.6K
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma06:15

Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma

Published on: October 27, 2014

27.4K

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...
3.8K
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...
3.5K
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...
6.4K
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...
7.5K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.3K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.3K