Transformation by RAS oncogene decreases the width of substrate-spread fibroblasts but not their length

Margarita A Kharitonova1, Pavel B Kopnin, Jury M Vasiliev

  • 1Institute of Carcinogenesis, Cancer Research Center of Russian Federation, Kashirskoye shosse 24, 115478 Moscow, Russian Federation. ritasarc@mail.ru

Insights

RAS oncogene transformation significantly reduces cell area but not projection length in mouse and rat fibroblasts. This indicates a selective impact on transversal spreading, increasing cell polarity.

Area of Science:

  • Cell biology
  • Oncology
  • Biophysics

Background:

  • Cell transformation is a key event in cancer development.
  • RAS oncogenes are frequently implicated in various cancers.
  • Understanding morphometric changes aids in characterizing transformed cells.

Purpose of the Study:

  • To compare morphometric parameters of non-transformed and RAS-transformed mouse and rat cell lines.
  • To investigate the specific effects of RAS oncogene transformation on cell shape and spreading.

Main Methods:

  • Comparative analysis of cell contours.
  • Morphometric measurements of cell area and projection length.
  • Utilizing four pairs of mouse and rat cell lines, both non-transformed and RAS-transformed.

Main Results:

  • RAS-transformed cell lines exhibited significantly smaller mean areas compared to non-transformed counterparts.
  • The average length of cell projections did not show a consistent decrease after RAS transformation.
  • Transformation selectively affected transversal spreading, not longitudinal spreading.

Conclusions:

  • RAS oncogene expression selectively impacts transversal cell spreading.
  • Transformed fibroblasts display altered morphometric properties, including increased antero-posterior polarity.
  • These findings contribute to understanding the biophysical basis of oncogenic transformation.

Related Concept Videos

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...
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...
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:
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...
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...
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...