Related Experiment Video

Updated: May 2, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

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

Published on: June 7, 2019

8.6K

Pten loss induces autocrine FGF signaling to promote skin tumorigenesis

Kristina Hertzler-Schaefer1, Grinu Mathew2, Ally-Khan Somani3

  • 1Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.

Cell Reports
|March 4, 2014
PubMed

Insights

Loss of the Pten tumor suppressor increases Fibroblast Growth Factor 10 (FGF10) protein, driving skin cancer through mTORC1 and FGF receptor signaling.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • The Phosphatidylinositol 3-kinase/mammalian Target of Rapamycin (PI3K-mTOR) pathway is crucial in cell growth and is often dysregulated in cancer.
  • PTEN (Phosphatase and tensin homolog) is a key tumor suppressor that negatively regulates the PI3K-mTOR pathway.

Purpose of the Study:

  • To investigate the molecular mechanisms by which PTEN loss promotes cutaneous squamous cell carcinoma (SCC).
  • To identify downstream effectors and signaling pathways activated by PTEN inactivation in skin cancer models.

Main Methods:

  • Utilized a mouse model of cutaneous SCC with Pten deletion.
  • Assessed Fgf10 protein and transcript levels in vitro and in vivo.
  • Investigated the role of mTORC1 complex and FGFR2 in Pten-mutant skin tumorigenesis.
  • Examined the effects of ectopic Fgf10 expression on skin papilloma formation.

Main Results:

  • Pten deletion significantly elevated Fgf10 protein levels without altering Fgf10 transcription.
  • Disruption of the mTORC1 complex reversed Fgf10 translational activation and prevented skin tumors in Pten mutants.
  • Ectopic Fgf10 expression induced skin papillomas.
  • Epidermal deletion of FGFR2 inhibited skin tumors in Pten-deficient mice.

Conclusions:

  • PTEN loss leads to increased Fgf10 protein via translational activation, mediated by mTORC1.
  • Autocrine activation of FGF signaling (FGF10/FGFR2 axis) is a critical driver of Pten-deficient skin tumorigenesis.
  • Targeting the FGF signaling pathway may offer therapeutic strategies for PTEN-deficient skin cancers.

More Related Videos

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells09:37

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

Published on: August 25, 2021

1.5K
Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA04:12

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA

Published on: December 19, 2019

14.4K

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...
3.6K
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...
5.1K
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...
7.2K
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...
6.3K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

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.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.9K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

1.7K