Related Experiment Video

Updated: Sep 5, 2025

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein
07:08

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein

Published on: January 16, 2020

5.8K

Mutant KRAS-Associated Proteome Is Mainly Controlled by Exogenous Factors

Patrícia Dias Carvalho1,2,3, Flávia Martins1,2,4, Joana Carvalho1,2

  • 1Instituto de Investigação e Inovação em Saúde (i3S), Rua Alfredo Allen 208, 4200-135 Porto, Portugal.

Cells
|July 9, 2022
PubMed

Insights

Mutant KRAS signaling is influenced by the tumor microenvironment, impacting colorectal cancer cell responses. Understanding these KRAS-non-autonomous mechanisms is key for developing new cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • Mutant KRAS signaling is crucial in colorectal cancer, but its modulation by external factors and resistance mechanisms remain incompletely understood.
  • Identifying KRAS-autonomous versus KRAS-non-autonomous signaling is vital for discovering new therapeutic targets in mutant KRAS cancers.

Purpose of the Study:

  • To investigate how mutant KRAS signaling in colorectal cancer cells responds to fibroblast-secreted factors.
  • To differentiate KRAS-autonomous and KRAS-non-autonomous mechanisms in response to tumor microenvironment stimuli.

Main Methods:

  • Proteomic analysis of two mutant KRAS colorectal cancer cell lines (HCT116 and LS174T) after KRAS silencing and treatment with rhTGFβ1-activated fibroblast secretome.
  • Assessment of KRAS-dependent and fibroblast-dependent proteome alterations.

Main Results:

  • Fibroblast-secreted factors induced cell line-specific proteome changes, with mutant KRAS governing a significant portion (43% in HCT116, 38% in LS174T).
  • A majority of KRAS-associated proteins were regulated in a KRAS-non-autonomous manner, dependent on fibroblast factors (67% in HCT116, 78% in LS174T).
  • KRAS-non-autonomous pathways differed between cell lines, involving proteoglycans in cancer, p53, and Rap1 signaling (HCT116) or cell-spreading and metabolism (LS174T).

Conclusions:

  • Mutant KRAS signaling is highly context-dependent, influenced significantly by the tumor microenvironment.
  • Therapeutic strategies for mutant KRAS cancers should consider the tumor microenvironment's role in modulating signaling pathways.
Keywords:
cancer-associated fibroblastscolorectal cancermutant KRASproteomic analysis

More Related Videos

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells09:20

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells

Published on: July 6, 2021

2.5K
Cell-Type Specific Protein Purification and Identification from Complex Tissues Using a Mutant Methionine tRNA Synthetase Mouse Line07:39

Cell-Type Specific Protein Purification and Identification from Complex Tissues Using a Mutant Methionine tRNA Synthetase Mouse Line

Published on: April 13, 2022

3.0K

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...
6.4K
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...
3.9K
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:
4.2K
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...
4.6K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
7.0K
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...
6.0K