Related Experiment Video

Updated: Jul 13, 2026

Spontaneous Murine Model of Anaplastic Thyroid Cancer
05:39

Spontaneous Murine Model of Anaplastic Thyroid Cancer

Published on: February 3, 2023

Overexpression of the S-phase kinase-associated protein 2 in thyroid cancer

Gennaro Chiappetta1, Carmela De Marco, Alfina Quintiero

  • 1Laboratorio Oncologia Sperimentale III, Istituto Nazionale Tumori, via M. Semmola, 80131 Napoli, Italy.

Endocrine-Related Cancer
|July 20, 2007
PubMed

Insights

S-phase kinase-associated protein 2 (Skp2) is overexpressed in thyroid cancer, leading to the degradation of the p27 protein. Skp2 overexpression drives thyroid cancer cell proliferation and development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Loss of the cyclin-dependent kinase inhibitor p27 expression via enhanced protein degradation is common in human cancers.
  • S-phase kinase-associated protein 2 (Skp2) mediates p27 ubiquitination and degradation.
  • The role of Skp2 in human thyroid tumors remains to be fully elucidated.

Purpose of the Study:

  • To investigate the role of Skp2 in the development of human thyroid tumors.
  • To analyze Skp2 expression levels in various types of thyroid lesions.
  • To determine the correlation between Skp2 and p27 expression and its functional impact on thyroid cancer cells.

Main Methods:

  • Immunohistochemistry to assess Skp2 and p27 protein expression in thyroid tissues.
  • Quantitative PCR (Q-PCR) and fluorescence in situ hybridization (FISH) to detect Skp2 gene amplification.
  • In vitro experiments to evaluate the effect of Skp2 suppression or forced expression on thyroid cancer cell proliferation.

Main Results:

  • Skp2 was significantly overexpressed in thyroid carcinomas compared to goitres and adenomas.
  • High Skp2 expression was more frequent in anaplastic thyroid carcinoma (ATC) than follicular (FTC) or papillary thyroid carcinoma (PTC).
  • Skp2 overexpression correlated inversely with p27 expression and was associated with increased p27 degradation activity.
  • Skp2 gene amplification was observed in a subset of thyroid cell lines and primary tumors.
  • Suppression of Skp2 reduced thyroid cancer cell proliferation, while its overexpression promoted proliferation and bypassed normal growth controls.

Conclusions:

  • Skp2 is frequently overexpressed and amplified in human thyroid cancer, particularly in ATC.
  • Skp2-mediated p27 degradation is a key mechanism driving thyroid cancer development and progression.
  • Skp2 represents a potential therapeutic target for thyroid cancer.

Related Concept Videos

Hyperthyroidism II: Pathophysiology01:27

Hyperthyroidism II: Pathophysiology

Hyperthyroidism is a hypermetabolic state caused by elevated levels of thyroid hormones, triiodothyronine (T3) and thyroxine (T4). It results from dysregulation at the thyroid, pituitary, or immune system level and affects multiple organ systems.PathophysiologyThe most common cause of hyperthyroidism is Graves’ disease, an autoimmune disorder in which antibodies, specifically thyroid-stimulating antibodies (TSAb), a subtype of TSH receptor antibodies (TRAb), bind to and activate TSH receptors...
Graves Disease II: Pathophysiology01:24

Graves Disease II: Pathophysiology

Graves’ disease is an autoimmune disorder characterized by the production of thyroid-stimulating immunoglobulins (TSI) that activate TSH receptors, leading to excessive synthesis and release of thyroid hormones (T3 and T4) and resulting in hyperthyroidism.Among all causes of hyperthyroidism, Graves’ disease is the most common and can happen at any age, though it is more frequent in women. It produces a hypermetabolic state with features such as weight loss, tachycardia, tremor, and heat...
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...
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 iodine is then...
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...
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...