RGD Reference Report - TGF-beta signaling alterations and susceptibility to colorectal cancer. - Rat Genome Database

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TGF-beta signaling alterations and susceptibility to colorectal cancer.

Authors: Xu, Y  Pasche, B 
Citation: Xu Y and Pasche B, Hum Mol Genet. 2007 Apr 15;16 Spec No 1:R14-20.
RGD ID: 2306282
Pubmed: PMID:17613544   (View Abstract at PubMed)
PMCID: PMC2637552   (View Article at PubMed Central)
DOI: DOI:10.1093/hmg/ddl486   (Journal Full-text)

In 2006, more than 55,000 patients died of colorectal cancer in the US, accounting for approximately 10% of all cancer deaths. Despite significant progress in screening combined with the development of novel effective therapies, colorectal cancer ranks second to lung cancer as a cause of cancer death. Twin studies indicate that 35% of all colorectal cancers are inherited, but high-penetrance tumor susceptibility genes only account for approximately 3-6% of all cases. The remainder of the unexplained familial risk is presumably due to other high-penetrance genes, but polygenic mechanisms and low-penetrance tumor susceptibility genes are likely to account for a greater proportion of familial colorectal cancers. In this regard, there is growing evidence that a common hypomorphic variant of the type I TGF-beta receptor, TGFBR1*6A, may account for approximately 3% of all colorectal cancer cases, a fraction higher than that attributable to mismatch repair genes MLH1, MSH2, MSH6 and PMS2. Furthermore, TGFBR1*6A is emerging as a potent modifier of colorectal cancer risk among individuals with a strong family of colorectal cancer. The TGF-beta signaling pathway plays a central but paradoxical role in the predisposition and progression of colorectal cancer. TGF-beta is a potent inhibitor of normal colonic epithelial cells acting as a tumor suppressor. However, TGF-beta promotes the survival, invasion and metastasis of colorectal cancer cells, thereby acting as an oncogene. Understanding how selective alterations of the TGF-beta signaling pathway contribute to colorectal cancer development and progression will likely permit the identification of an additional fraction of inherited colorectal cancer cases and provide novel opportunities for therapeutic intervention.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TGFBR1HumanLynch syndrome  IAGP  RGD 
Tgfbr1RatLynch syndrome  ISOTGFBR1 (Homo sapiens) RGD 
Tgfbr1MouseLynch syndrome  ISOTGFBR1 (Homo sapiens) RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SMAD2Humanaltered transforming growth factor-beta Smad dependent signaling pathway   TAS  RGD 
SMAD3Humanaltered transforming growth factor-beta Smad dependent signaling pathway   TAS  RGD 
SMAD4Humanaltered transforming growth factor-beta Smad dependent signaling pathway   TAS  RGD 
Smad2Mousealtered transforming growth factor-beta Smad dependent signaling pathway   ISOSMAD2 (Homo sapiens) RGD 
Smad2Rataltered transforming growth factor-beta Smad dependent signaling pathway   ISOSMAD2 (Homo sapiens) RGD 
Smad3Mousealtered transforming growth factor-beta Smad dependent signaling pathway   ISOSMAD3 (Homo sapiens) RGD 
Smad3Rataltered transforming growth factor-beta Smad dependent signaling pathway   ISOSMAD3 (Homo sapiens) RGD 
Smad4Mousealtered transforming growth factor-beta Smad dependent signaling pathway   ISOSMAD4 (Homo sapiens) RGD 
Smad4Rataltered transforming growth factor-beta Smad dependent signaling pathway   ISOSMAD4 (Homo sapiens) RGD 
TGFB1Humanaltered transforming growth factor-beta Smad dependent signaling pathway   TAS  RGD 
TGFBR1Humanaltered transforming growth factor-beta Smad dependent signaling pathway   TAS  RGD 
TGFBR2Humanaltered transforming growth factor-beta Smad dependent signaling pathway   TAS  RGD 
Tgfb1Mousealtered transforming growth factor-beta Smad dependent signaling pathway   ISOTGFB1 (Homo sapiens) RGD 
Tgfb1Rataltered transforming growth factor-beta Smad dependent signaling pathway   ISOTGFB1 (Homo sapiens) RGD 
Tgfbr1Mousealtered transforming growth factor-beta Smad dependent signaling pathway   ISOTGFBR1 (Homo sapiens) RGD 
Tgfbr1Rataltered transforming growth factor-beta Smad dependent signaling pathway   ISOTGFBR1 (Homo sapiens) RGD 
Tgfbr2Rataltered transforming growth factor-beta Smad dependent signaling pathway   ISOTGFBR2 (Homo sapiens) RGD 
Tgfbr2Mousealtered transforming growth factor-beta Smad dependent signaling pathway   ISOTGFBR2 (Homo sapiens) RGD 
SMAD2Humancolorectal cancer pathway   TAS  RGD 
SMAD3Humancolorectal cancer pathway   TAS  RGD 
SMAD4Humancolorectal cancer pathway   TAS  RGD 
Smad2Ratcolorectal cancer pathway   ISOSMAD2 (Homo sapiens) RGD 
Smad2Mousecolorectal cancer pathway   ISOSMAD2 (Homo sapiens) RGD 
Smad3Ratcolorectal cancer pathway   ISOSMAD3 (Homo sapiens) RGD 
Smad3Mousecolorectal cancer pathway   ISOSMAD3 (Homo sapiens) RGD 
Smad4Ratcolorectal cancer pathway   ISOSMAD4 (Homo sapiens) RGD 
Smad4Mousecolorectal cancer pathway   ISOSMAD4 (Homo sapiens) RGD 
TGFB1Humancolorectal cancer pathway   TAS  RGD 
TGFBR1Humancolorectal cancer pathway   TAS  RGD 
TGFBR2Humancolorectal cancer pathway   TAS  RGD 
Tgfb1Ratcolorectal cancer pathway   ISOTGFB1 (Homo sapiens) RGD 
Tgfb1Mousecolorectal cancer pathway   ISOTGFB1 (Homo sapiens) RGD 
Tgfbr1Mousecolorectal cancer pathway   ISOTGFBR1 (Homo sapiens) RGD 
Tgfbr1Ratcolorectal cancer pathway   ISOTGFBR1 (Homo sapiens) RGD 
Tgfbr2Ratcolorectal cancer pathway   ISOTGFBR2 (Homo sapiens) RGD 
Tgfbr2Mousecolorectal cancer pathway   ISOTGFBR2 (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Smad2  (SMAD family member 2)
Smad3  (SMAD family member 3)
Smad4  (SMAD family member 4)
Tgfb1  (transforming growth factor, beta 1)
Tgfbr1  (transforming growth factor, beta receptor 1)
Tgfbr2  (transforming growth factor, beta receptor 2)

Genes (Mus musculus)
Smad2  (SMAD family member 2)
Smad3  (SMAD family member 3)
Smad4  (SMAD family member 4)
Tgfb1  (transforming growth factor, beta 1)
Tgfbr1  (transforming growth factor, beta receptor I)
Tgfbr2  (transforming growth factor, beta receptor II)

Genes (Homo sapiens)
SMAD2  (SMAD family member 2)
SMAD3  (SMAD family member 3)
SMAD4  (SMAD family member 4)
TGFB1  (transforming growth factor beta 1)
TGFBR1  (transforming growth factor beta receptor 1)
TGFBR2  (transforming growth factor beta receptor 2)


Additional Information