We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
PURITAN MEDICAL

Download Mobile App




Disrupted TGFB Signaling Linked to Increased Cancer-Related Bacteria

By LabMedica International staff writers
Posted on 14 Oct 2019
Following careful analysis of DNA sequences collected in The Cancer Genome Atlas, researchers have proposed that CEACAM (carcinoembryonic antigen related cell adhesion molecule) proteins disrupt TGFB signaling, which alters the composition of the intestinal microbiome to promote development of colorectal cancer.

The TGFB (transforming growth factor beta) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, apoptosis, cellular homeostasis, and other cellular functions. More...
In spite of the wide range of cellular processes that the TGFB signaling pathway regulates, the process is relatively simple. TGFB superfamily ligands bind to a type II receptor, which recruits and phosphorylates a type I receptor. The type I receptor then phosphorylates receptor-regulated SMAD proteins (R-SMADs), which binds the coSMAD SMAD4. R-SMAD/coSMAD complexes accumulate in the nucleus where they act as transcription factors and participate in the regulation of target gene expression.

Investigators at George Washington University (Washington, DC, USA) studied interactions among proteins of the CEACAM family, which interact with microbes and the transforming growth factor beta (TGFB) signaling pathway, which is often altered in colorectal cancer cells. They investigated mechanisms by which CEACAM proteins inhibit TGFB signaling and alter the intestinal microbiome to promote development of colorectal cancer.

For this study, the investigators collected data on DNA sequences, mRNA expression levels, and patient survival times from 456 colorectal adenocarcinoma cases, and a separate set of 594 samples of colorectal adenocarcinomas, in the Cancer Genome Atlas. The Cancer Genome Atlas is a project, begun in 2005, to catalog genetic mutations responsible for cancer, using genome sequencing and bioinformatics. The Cancer Genome Atlas applies high-throughput genome analysis techniques to improve diagnosis, treatment, and prevention of cancer through a better understanding of the genetic basis of this disease.

Results revealed that in colorectal adenocarcinomas, high expression levels of genes encoding CEACAM proteins, especially CEACAM5, were associated with reduced survival times of patients. There was an inverse correlation between expression of CEACAM genes and expression of TGFB pathway genes (TGFBR1, TGFBR2, and SMAD3). In colorectal adenocarcinomas, they also found an inverse correlation between expression of genes in the TGFB signaling pathway and genes that regulate stem cell features of cells. They found mutations encoding L640I and A643T in the B3 domain of human CEACAM5 in colorectal adenocarcinomas; structural studies indicated that these mutations would alter the interaction between CEACAM5 and TGFBR1.

These findings from human cancer patients were reinforced by data from animal studies, which showed that compared with feces from wild-type mice, feces from mice with defects in TGFB signaling had increased abundance of bacterial species that have been associated with the development of colon tumors.

“Colon cancer is increasing in young people. Current guidelines recommend screening those over age 50 for colon cancer, but today we are seeing that 15% of those with colon cancer are under the age of 50,” said senior author Dr. Lopa Mishra, professor of surgery at the George Washington University. “We hypothesized that diet and its effects on the microbiome may be big players, which is where we focused our study.”

The CEACAM protein study was published in the October 1, 2019, online edition of the journal Gastroenterology.

Related Links:
George Washington University


New
Gold Member
Cardiovascular Risk Test
Metabolic Syndrome Array I & II
3-Part Differential Hematology Analyzer
Swelab Alfa Plus Sampler
New
Specimen Radiography System
TrueView 200 Pro
New
8-Channel Pipette
SAPPHIRE 20–300 µL
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








DIASOURCE (A Biovendor Company)

Channels

Molecular Diagnostics

view channel
Image: A diagnostic test can distinguish patients with head and neck squamous cell carcinoma who can be cured with surgery alone (Photo courtesy of University of Turku)

Novel Diagnostic Tool to Revolutionize Treatment Guidance of Head and Neck Cancer

Head and neck squamous cell carcinoma (HNSCC) is a solid tumor type commonly treated with surgery. However, there has been no clinically available method to determine which patients can be cured with surgery... Read more

Hematology

view channel
Image: The microfluidic device for passive separation of platelet-rich plasma from whole blood (Photo courtesy of University of the Basque Country)

Portable and Disposable Device Obtains Platelet-Rich Plasma Without Complex Equipment

Platelet-rich plasma (PRP) plays a crucial role in regenerative medicine due to its ability to accelerate healing and repair tissue. However, obtaining PRP traditionally requires expensive centrifugation... Read more

Immunology

view channel
Image: The 3D paper-based analytical device has shown high clinical accuracy for adult-onset immunodeficiency (Photo courtesy of National Taiwan University)

Paper-Based Device Accurately Detects Immune Defects in 10 Minutes

Patients with hidden immune defects are especially vulnerable to severe and persistent infections, often due to autoantibodies that block interferon-gamma (IFN-γ), a key molecule in immune defense.... Read more

Microbiology

view channel
Image: The groundbreaking salmonella antimicrobial resistance prediction platform has demonstrated 95% accuracy (Photo courtesy of Yujie You et al., DOI: 10.1016/j.eng.2025.01.013)

New Platform Leverages AI and Quantum Computing to Predict Salmonella Antimicrobial Resistance

Antimicrobial-resistant Salmonella strains are a growing public health concern due to the overuse of antimicrobials and the rise of genetic mutations. Accurate prediction of resistance is crucial for effective... Read more

Technology

view channel
Image: The Check4 gene-detection platform (Photo courtesy of IdentifySensors)

Electronic Biosensors Used to Detect Pathogens Can Rapidly Detect Cancer Cells

A major challenge in healthcare is the early and affordable detection of serious diseases such as cancer. Early diagnosis remains difficult due to the complexity of identifying specific genetic markers... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.