Related Experiment Video

Updated: Nov 3, 2025

An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
07:01

An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma

Published on: April 17, 2013

21.3K

BRAF Inhibitors Induce Feedback Activation of RAS Pathway in Thyroid Cancer Cells

Elisa Bonaldi1, Chiara Gargiuli2, Loris De Cecco2

  • 1Molecular Mechanisms Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.

International Journal of Molecular Sciences
|June 2, 2021
PubMed

Insights

BRAF inhibitors like Vemurafenib and Dabrafenib show antiproliferative and redifferentiative effects in papillary thyroid cancer (PTC) cell lines. These BRAF inhibitors also rewire the MAPK pathway, offering insights into targeted therapy response mechanisms.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • BRAF mutations are common in papillary thyroid cancer (PTC).
  • BRAF inhibitors are used for treatment-resistant PTC, but resistance mechanisms are unclear.
  • Understanding BRAF inhibitor response is crucial for optimizing targeted therapies in thyroid cancer.

Purpose of the Study:

  • To investigate the effects of Vemurafenib and Dabrafenib on BRAF-mutated thyroid cancer (TC) cell lines.
  • To explore the mechanisms underlying BRAF inhibitor response in TC.
  • To analyze gene expression and pathway modulation following targeted therapy.

Main Methods:

  • Treatment of BRAF-mutated TC cell lines with Vemurafenib and Dabrafenib.
  • Assessment of cell proliferation and NIS transporter activity.
  • Global gene expression analysis using microarrays and gene set enrichment analysis (GSEA).

Main Results:

  • Both BRAF inhibitors demonstrated antiproliferative and redifferentiative effects on TC cells.
  • Treatment led to a rewiring of the MAPK pathway, with increased RAS signaling.
  • Gene expression analysis revealed modulation of pathways related to MAPK activation and thyroid differentiation.

Conclusions:

  • Vemurafenib and Dabrafenib induce significant anti-cancer effects in BRAF-mutated TC.
  • A MAPK pathway rewiring towards RAS signaling is a key response mechanism.
  • Findings provide insights into targeted therapy response in thyroid cancer, aligning with recent clinical observations.
Keywords:
BRAF inhibitorsBRAFV600Ecell signalingthyroid cancer cell

More Related Videos

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity09:31

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity

Published on: October 17, 2025

90
Spontaneous Murine Model of Anaplastic Thyroid Cancer05:39

Spontaneous Murine Model of Anaplastic Thyroid Cancer

Published on: February 3, 2023

1.9K

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.6K
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...
4.0K
Synthesis and Regulation of Thyroid Hormones01:20

Synthesis and Regulation of Thyroid Hormones

Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
6.0K
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...
6.8K
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...
4.3K
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...
6.8K