Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

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...
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...
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 are of three kinds RI, RII, and RIII. The RI...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Lineage and organ signals sequentially build organ intrinsic nervous systems.

Nature·2026
Same author

Discoidin Domain Receptor 1 Translocation to the Mitochondria Promotes Oxidative Stress and Apoptosis in Acute Kidney Injury.

Journal of the American Society of Nephrology : JASN·2026
Same author

Kindlins regulate integrin- and growth factor-dependent ureteric bud formation.

Development (Cambridge, England)·2026
Same author

α-Parvin promotes glucose uptake and metabolism in skeletal muscle with minimal influence on hepatic insulin sensitivity.

Molecular metabolism·2026
Same author

Integrin α 1 β 1 Promotes Interstitial Fibrosis and Cyst Growth in a Mouse Model of Polycystic Kidney Disease.

Journal of the American Society of Nephrology : JASN·2026
Same author

α-Parvin regulation of cell re-arrangement is critical for ureteric bud branching morphogenesis.

bioRxiv : the preprint server for biology·2025

Related Experiment Video

Updated: Jul 13, 2026

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
04:12

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

Published on: December 19, 2019

Signaling pathways regulating TC21-induced tumorigenesis.

Mete Erdogan1, Ambra Pozzi, Neil Bhowmick

  • 1Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

The Journal of Biological Chemistry
|July 28, 2007
PubMed
Summary

TC21 (R-Ras2) overexpression drives cancer progression by activating key signaling pathways like PI3K and mTOR. These transformed cells become resistant to TGF-beta

More Related Videos

Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia
08:14

Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia

Published on: July 25, 2017

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Related Experiment Videos

Last Updated: Jul 13, 2026

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
04:12

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

Published on: December 19, 2019

Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia
08:14

Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia

Published on: July 25, 2017

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • TC21 (R-Ras2) is a Ras-related GTPase involved in human cancer pathogenesis.
  • Transforming growth factor beta (TGF-beta) has complex roles in tumorigenesis, inhibiting normal cells but promoting proliferation in Ras-transformed cells.
  • The precise mechanisms of TC21-induced tumor formation and TGF-beta's regulation of TC21-transformed cells remain unclear.

Purpose of the Study:

  • To investigate the role of TC21 in cancer progression.
  • To elucidate the signaling pathways mediating TC21-induced transformation.
  • To determine how TGF-beta affects TC21-transformed cells.

Main Methods:

  • Overexpression of an activated G23V mutant of TC21 in EpH4 murine mammary epithelial cells.
  • In vitro and in vivo oncogenicity assays.
  • Analysis of signaling pathway activation (p38 MAPK, mTOR, PI3K, Akt/PKB) and TGF-beta response.

Main Results:

  • Mutant TC21-expressing cells exhibited significantly higher oncogenicity than those expressing activated H-Ras.
  • TC21-induced transformation and proliferation were dependent on p38 MAPK, mTOR, and phosphoinositide 3-kinase activation, but not Akt/PKB.
  • TC21-transformed cells became insensitive to TGF-beta's growth inhibitory effects, with increased soft agar growth upon TGF-beta stimulation.
  • Smad-dependent and independent pathways remained functional despite loss of TGF-beta growth inhibition response.

Conclusions:

  • Overexpression of active TC21 promotes tumorigenicity via the PI3K, p38 MAPK, and mTOR pathways.
  • TC21 transformation confers resistance to the normal growth-inhibitory functions of TGF-beta.
  • Understanding these pathways is crucial for targeting TC21 in cancer therapy.