Related Experiment Video

Updated: Jun 25, 2026

Spontaneous Murine Model of Anaplastic Thyroid Cancer
05:39

Spontaneous Murine Model of Anaplastic Thyroid Cancer

Published on: February 3, 2023

Gal-3 is stimulated by gain-of-function p53 mutations and modulates chemoresistance in anaplastic thyroid carcinomas

Luca Lavra1, Alessandra Ulivieri, Cinzia Rinaldo

  • 1S. Pietro Fatebenefratelli Hospital, Rome, Italy.

The Journal of Pathology
|February 10, 2009
PubMed

Insights

Gain-of-function p53 mutations in thyroid cancer stimulate Galectin-3 (Gal-3) expression, increasing chemoresistance. Inhibiting Gal-3 enhances sensitivity to chemotherapy in anaplastic thyroid carcinomas.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Galectin-3 (Gal-3) is an anti-apoptotic protein.
  • Wild-type p53 (wt-p53) normally down-regulates Gal-3, promoting apoptosis.
  • Thyroid carcinomas, particularly PDTCs and ATCs, often have p53 mutations.

Purpose of the Study:

  • To investigate the influence of p53 mutations on Gal-3 expression and activity in thyroid cancers.
  • To determine if altered Gal-3 expression contributes to chemoresistance in anaplastic thyroid carcinomas.

Main Methods:

  • Analysis of Gal-3 expression in human thyroid tissues and cell lines with varying p53 mutation status.
  • Over-expression and knockdown experiments of p53 (wild-type and mutant R273H) in thyroid carcinoma cell lines.
  • Assessment of chemosensitivity following Gal-3 interference in resistant cell lines.

Main Results:

  • A positive correlation was observed between Gal-3 expression and p53 mutations in thyroid tissues and cell lines.
  • Gal-3 was over-expressed in anaplastic thyroid carcinomas and cell lines, especially those with the p53(R273H) mutation.
  • Mutant p53 (p53(R273H)) stimulated Gal-3 expression, while wt-p53 inhibited it.
  • Interference with Gal-3 expression in chemoresistant cells increased their sensitivity to cisplatin.

Conclusions:

  • Gain-of-function p53 mutants acquire the ability to up-regulate Gal-3 expression.
  • Increased Gal-3 expression driven by mutant p53 contributes to chemoresistance in anaplastic thyroid carcinomas.
  • Targeting Gal-3 may represent a therapeutic strategy to overcome chemoresistance in these cancers.

More Related Videos

Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma06:08

Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma

Published on: June 2, 2023

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 daughter...
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...
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...
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...