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New intracellular and molecular aspects in pathophysiology of colorectal cancer.

Ziapour P, Ataee R, Shadifar M, Vaillancourt C, Ahmadi A, Jafari-Sabet M, Ataee A - Gastroenterol Hepatol Bed Bench (2011)

Bottom Line: Colorectal cancer is one of the most common malignancy in the world and the second cancer-related death, many molecular and genetic aspects of this disease have been cleared as chromosomal instability and the role of some key proteins as WNT/β catenin, trypsin and others.Also recently the role of folate turnover and some neurotransmitters as serotonin were also considered.The scope of this review is to describe some details about new molecular pathways suggested for occurrence or progress of this disease.

View Article: PubMed Central - PubMed

Affiliation: Cell and Molecular Research Lab, Amol Research Center, Pasteur Institute of Iran, Amol, Iran ; Parasitiology Department, Amol Research Center, Pasteur Institute of Iran, Amol, Iran.

ABSTRACT
Colorectal cancer is one of the most common malignancy in the world and the second cancer-related death, many molecular and genetic aspects of this disease have been cleared as chromosomal instability and the role of some key proteins as WNT/β catenin, trypsin and others. Also recently the role of folate turnover and some neurotransmitters as serotonin were also considered. The scope of this review is to describe some details about new molecular pathways suggested for occurrence or progress of this disease.

No MeSH data available.


Related in: MedlinePlus

Simplified model showing current knowledge of trypsin interaction with proteinase-activated receptor 2 (PAR-2) and the matrix metalloproteinase (MMPs). The arrows indicate activation (52).
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Figure 0003: Simplified model showing current knowledge of trypsin interaction with proteinase-activated receptor 2 (PAR-2) and the matrix metalloproteinase (MMPs). The arrows indicate activation (52).

Mentions: Trypsin is one of characterized serine proteinases. Proteinases play essential roles not only in many physiological processes (eg food digestion, blood coagulation, fibrinolysis, and control of blood pressure) but also in a wide range of important pathological processes (eg atherosclerosis, inflammation and cancer) (31, 32). Trypsin exhibits selective proteolytic activity against the peptide bonds in protein molecules that have carboxyl groups donated by the amino acids arginine and lysine. For physiological protection against premature activity, as known from pancreatic physiology, trypsin is secreted as an inactive zymogen (trypsinogen) in the pancreatic juice, and is activated by conversion to trypsin by an enteropeptidase in the alkaline milieu of the duodenal lumen. Secondly, trypsinogen may be activated into active trypsin by an enteropeptidase found in duodenal enterocytes (33, 34). Interestingly,adenocarcinoma cells of the duodenum (32), as well as other tissues expressing trypsin, have a trypsin-activating enteropeptidase (29, 30). Lastly, the antiproteinase mediator pancreatic secretory trypsin inhibitor (PSTI) protects from premature activity. An imbalance in this ‘proteinase–antiproteinase-system’ plays a pathophysiological role in the development of pancreatitis and seems to present an increased risk for developing pancreatic adenocarcinoma (29–31) PSTI is excreted by the mucosa of the normal gastrointestinal tract, where it serves to protect the cells from proteolytic breakdown. The same peptide is secreted by tumour cells, and is often referred to as ‘tumour associated trypsin inhibitor’ (TATI), which is identical to PSTI. Trypsin expression is increased in human cancer cells of the ovary, prostate, lung, stomach, colon, and others. Trypsin in cancer is often referred to as ‘tumour-associated trypsin’, and generally represents trypsin-1 and trypsin-2 (35). The contributing role of the tumor environment and its constituents (ie stroma cells, signal molecules, matrix enzymes) in the invasive and metastatic process is emerging (Figure2, 3) (36). Recently evidence declare that the adverse effects of trypsin are mediated through interplay with other proteinases systems (Figure 3), such as the MMPs (37) and the recently explored PAR-2 (37–40). The current a mechanism by which trypsin induces invasion and metastasis are manifold. Firstly, as a proteolytic enzyme, trypsin may directly degrade extracellular proteins by itself, by attacking type 1 collagen of the basal membrane (39). Secondly, its effect is likely to be mediated indirectly through the activation and effect of other latent proteolytic cascades, the most important being the MMPs. Lastly, recent evidence points to the activation of signal molecules, such as PAR-2.


New intracellular and molecular aspects in pathophysiology of colorectal cancer.

Ziapour P, Ataee R, Shadifar M, Vaillancourt C, Ahmadi A, Jafari-Sabet M, Ataee A - Gastroenterol Hepatol Bed Bench (2011)

Simplified model showing current knowledge of trypsin interaction with proteinase-activated receptor 2 (PAR-2) and the matrix metalloproteinase (MMPs). The arrows indicate activation (52).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4017408&req=5

Figure 0003: Simplified model showing current knowledge of trypsin interaction with proteinase-activated receptor 2 (PAR-2) and the matrix metalloproteinase (MMPs). The arrows indicate activation (52).
Mentions: Trypsin is one of characterized serine proteinases. Proteinases play essential roles not only in many physiological processes (eg food digestion, blood coagulation, fibrinolysis, and control of blood pressure) but also in a wide range of important pathological processes (eg atherosclerosis, inflammation and cancer) (31, 32). Trypsin exhibits selective proteolytic activity against the peptide bonds in protein molecules that have carboxyl groups donated by the amino acids arginine and lysine. For physiological protection against premature activity, as known from pancreatic physiology, trypsin is secreted as an inactive zymogen (trypsinogen) in the pancreatic juice, and is activated by conversion to trypsin by an enteropeptidase in the alkaline milieu of the duodenal lumen. Secondly, trypsinogen may be activated into active trypsin by an enteropeptidase found in duodenal enterocytes (33, 34). Interestingly,adenocarcinoma cells of the duodenum (32), as well as other tissues expressing trypsin, have a trypsin-activating enteropeptidase (29, 30). Lastly, the antiproteinase mediator pancreatic secretory trypsin inhibitor (PSTI) protects from premature activity. An imbalance in this ‘proteinase–antiproteinase-system’ plays a pathophysiological role in the development of pancreatitis and seems to present an increased risk for developing pancreatic adenocarcinoma (29–31) PSTI is excreted by the mucosa of the normal gastrointestinal tract, where it serves to protect the cells from proteolytic breakdown. The same peptide is secreted by tumour cells, and is often referred to as ‘tumour associated trypsin inhibitor’ (TATI), which is identical to PSTI. Trypsin expression is increased in human cancer cells of the ovary, prostate, lung, stomach, colon, and others. Trypsin in cancer is often referred to as ‘tumour-associated trypsin’, and generally represents trypsin-1 and trypsin-2 (35). The contributing role of the tumor environment and its constituents (ie stroma cells, signal molecules, matrix enzymes) in the invasive and metastatic process is emerging (Figure2, 3) (36). Recently evidence declare that the adverse effects of trypsin are mediated through interplay with other proteinases systems (Figure 3), such as the MMPs (37) and the recently explored PAR-2 (37–40). The current a mechanism by which trypsin induces invasion and metastasis are manifold. Firstly, as a proteolytic enzyme, trypsin may directly degrade extracellular proteins by itself, by attacking type 1 collagen of the basal membrane (39). Secondly, its effect is likely to be mediated indirectly through the activation and effect of other latent proteolytic cascades, the most important being the MMPs. Lastly, recent evidence points to the activation of signal molecules, such as PAR-2.

Bottom Line: Colorectal cancer is one of the most common malignancy in the world and the second cancer-related death, many molecular and genetic aspects of this disease have been cleared as chromosomal instability and the role of some key proteins as WNT/β catenin, trypsin and others.Also recently the role of folate turnover and some neurotransmitters as serotonin were also considered.The scope of this review is to describe some details about new molecular pathways suggested for occurrence or progress of this disease.

View Article: PubMed Central - PubMed

Affiliation: Cell and Molecular Research Lab, Amol Research Center, Pasteur Institute of Iran, Amol, Iran ; Parasitiology Department, Amol Research Center, Pasteur Institute of Iran, Amol, Iran.

ABSTRACT
Colorectal cancer is one of the most common malignancy in the world and the second cancer-related death, many molecular and genetic aspects of this disease have been cleared as chromosomal instability and the role of some key proteins as WNT/β catenin, trypsin and others. Also recently the role of folate turnover and some neurotransmitters as serotonin were also considered. The scope of this review is to describe some details about new molecular pathways suggested for occurrence or progress of this disease.

No MeSH data available.


Related in: MedlinePlus