Related Experiment Video

Updated: Mar 12, 2026

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

2.2K

Targeting of Ras-mediated FGF signaling suppresses Pten-deficient skin tumor

Grinu Mathew1,2, Abdul Hannan1,2, Kristina Hertzler-Schaefer3

  • 1Department of Ophthalmology, Columbia University, New York, NY 10032.

Proceedings of the National Academy of Sciences of the United States of America
|November 2, 2016
PubMed

Insights

Loss of PTEN (phosphatase and tensin homolog deleted on chromosome 10) in skin cells triggers FGF signaling, leading to hyperplasia. Targeting the Ras-MAPK pathway offers a potential therapy for PTEN-related skin tumors.

Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology

Background:

  • PTEN deficiency is linked to PTEN hamartoma tumor syndrome and various cancers.
  • Loss of Pten in skin keratinocytes induces autocrine FGF signaling.

Purpose of the Study:

  • To investigate the molecular mechanisms driving skin hyperplasia in Pten-deficient epidermis.
  • To identify key signaling pathways and potential therapeutic targets.

Main Methods:

  • Utilized genetic models of Pten deficiency in mouse skin.
  • Investigated the roles of Frs2α, Shp2, Ras, and PI3K pathways.
  • Employed genetic and pharmacological inhibition of the Ras-MAPK pathway.

Main Results:

  • Skin hyperplasia in Pten-deficient mice requires Frs2α and Shp2, upstream regulators of Ras signaling.
  • PI3-kinase catalytic subunit p110α interacts with Ras to promote hyperplasia, indicating Ras-PI3K cross-talk.
  • Inhibition of the Ras-MAPK pathway effectively reduced epidermal hyperplasia in Pten-deficient animals.

Conclusions:

  • A positive feedback loop exists between PTEN and Ras pathways in skin epidermis.
  • The FGF-activated Ras-MAPK pathway is a promising therapeutic target for PTEN-related skin tumors.
Keywords:
ErkFGFPtenRasskin

More Related Videos

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

9.6K
The Three-Dimensional Human Skin Reconstruct Model: a Tool to Study Normal Skin and Melanoma Progression11:02

The Three-Dimensional Human Skin Reconstruct Model: a Tool to Study Normal Skin and Melanoma Progression

Published on: August 3, 2011

51.1K

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...
5.0K
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...
5.4K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.9K
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...
7.4K
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...
8.3K
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...
6.1K