Related Experiment Video

Updated: Jul 7, 2026

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

Oncogenic Ras-induced morphologic change is through MEK/ERK signaling pathway to downregulate Stat3 at a

Hsuan-Heng Yeh1, Chin-Han Wu, Raghavaraju Giri

  • 1Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.

Neoplasia (New York, N.Y.)
|January 31, 2008
PubMed

Insights

Overexpression of Ha-ras(V12) triggers cell shape changes by reducing Signal transducer and activator of transcription 3 (Stat3) protein levels via proteasome degradation, impacting the MEK/ERK pathway.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Ras proteins are crucial regulators of cell signaling pathways, including the MAP kinase cascade.
  • Aberrant Ras signaling is implicated in various cancers and can induce significant cellular morphologic alterations.
  • Signal transducer and activator of transcription 3 (Stat3) is a key transcription factor activated by cytokines and involved in cell growth and survival.

Purpose of the Study:

  • To investigate the relationship between Ha-ras(V12) overexpression and Signal transducer and activator of transcription 3 (Stat3) protein expression.
  • To elucidate the mechanisms by which Ha-ras(V12) influences Stat3 levels and cellular morphology.
  • To determine the role of Stat3 in Ha-ras(V12)-induced morphologic changes.

Main Methods:

  • Utilized NIH3T3 cells overexpressing Ha-ras(V12).
  • Investigated Stat3 protein expression and degradation pathways (proteasome, mTOR/p70S6K).
  • Analyzed the involvement of the mitogen extracellular kinase (MEK)/extracellular-regulated kinase (ERK) signaling pathway and microtubule dynamics.

Main Results:

  • Ha-ras(V12) overexpression led to a posttranslational downregulation of Stat3 protein in NIH3T3 cells.
  • Stat3 downregulation occurred via proteasome degradation, independent of the mTOR/p70S6K pathway.
  • Ha-ras(V12)-induced morphologic changes and Stat3 suppression were mediated by the MEK/ERK pathway.
  • Microtubule disruption contributed to Ha-ras(V12)-induced morphologic changes, and Stat3 overexpression could reverse these effects.

Conclusions:

  • Stat3 protein plays a critical role in mediating Ha-ras(V12)-induced cellular morphologic changes.
  • Oncogenic Ras triggers morphologic alterations through MEK/ERK activation, leading to posttranslational downregulation of Stat3.
  • These findings offer insights into potential therapeutic strategies for Ras-related tumorigenesis.

More Related Videos

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells11:42

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells

Published on: April 7, 2017

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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 superfamily...
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...
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 rapamycin-insensitive companion...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity: