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Current Colorectal Cancer Reports

, Volume 8, Issue 4, pp 277–289 | Cite as

Progastrin Peptides Increase the Risk of Developing Colonic Tumors: Impact on Colonic Stem Cells

  • Pomila SinghEmail author
  • Shubhashish Sarkar
  • Carla Kantara
  • Carrie Maxwell
Molecular Biology (S Anant, Section Editor)

Abstract

Preneoplastic lesions (aberrant crypt foci, hyperplastic/dysplastic polyps) are believed to be precursors of sporadic colorectal tumors (adenomas, adenocarcinomas). Aberrant crypt foci and hyperplastic/dysplastic polyps likely originate from abnormal growth of colonic crypts in response to aberrant queues in the microenvironment of colonic crypts. Thus, identifying factors which regulate homeostatic versus aberrant proliferation/apoptosis of colonocytes, especially stem/progenitor cells, may lead to effective preventative/treatment strategies. On the basis of this philosophy, the role of growth factors/peptide hormones potentially available in the circulation/microenvironment of colonic crypts is being examined extensively. Since the time gastrins were discovered as trophic (growth) factors for gastrointestinal cells, the effect of gastrins on the growth of normal/cancer cells has been investigated, leading to many discoveries. Seminal discoveries in the area of gastrins and colon cancer as it relates to molecular pathways associated with formation of colonic tumors are reviewed and the possible impact on diagnostic/preventative/treatment strategies is discussed.

Keywords

Aberrant crypt foci Adenomas adenocarcinomas Akt Cell-surface-associated annexin A2 Cancer-stem cells β-Catenin Cluster of differentiation 44 Cluster of differentiation 133, CpG island methylator phenotype Chromosomal instability Colonic crypts Colorectal cancer Colon carcinogenesis Curcumin Cytochrome c oxidase subunit Vb Doublecortin–Ca+2/calmodulin kinase like protein Extracellular-signal-regulated kinases Hyperplastic polyps Janus kinase Leucine-rich-repeat-containing G-protein-coupled-receptor 5 Microsatellite-instability Nuclear factor κB p38 mitogen-activated protein kinase Progastrin/glycine-extended gastrin Phosphoinositide 3-kinase Rous Sarcoma viral gene encoded kinase Signal transducer and activator of transcription 3 

Abbreviations

ANXA2

Annexin A2

AOM

Azoxymethane

CCK

Cholecystokinin

CCK2R

Cholecystokinin type 2 receptor

CME

Clathrin-mediated endocytosis

CoxVb

Cytochrome c oxidase subunit Vb

CRC

Colorectal cancer

CS-ANXA2

Cell-surface-associated annexin A2

DCLK1

Doublecortin–Ca+2/calmodulin kinase like protein 1

EGF

Epidermal growth factor

EGFR

Epidermal growth factor receptor

ERK

Extracellular-signal-regulated kinase

Fabp-PG mice

Mice overexpressing human progastrin in the intestines in response to fatty acid binding proteins

G-Gly

Glycine-extended gastrin

hGAS mice

Mice constitutively overexpressing human progastrin

IGF

Insulin-like growth factor

INS-GAS mice

Mice overexpressing amidated gastrins in response to insulin

Lgr5

Leucine-rich-repeat-containing G-protein-coupled receptor 5

MAPK

Mitogen-activated protein kinase

MMP

Matrix metalloproteinase

NFκB

Nuclear factor κB

PI3K

Phosphoinositide-3-kinase

STAT3

Signal transducer and activator of transcription 3

Notes

Acknowledgments

P. Singh is supported by NIH grant RO1-CA97959-(9). The authors thank Cheryl Simmons for her valuable secretarial help in preparing the manuscript and Claiborne Fant for helping with the graphic design of the figure.

Disclosure

P. Singh: patent regarding vaccine against prograstrin pending (technology associated with the vaccine has been licensed by BioRéalités SAS, with licensing fees received by University of Texas Medical Branch); S. Sarkar: none; C. Kantara: none; C. Maxwell: none.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Pomila Singh
    • 1
    Email author
  • Shubhashish Sarkar
    • 1
  • Carla Kantara
    • 1
  • Carrie Maxwell
    • 1
  1. 1.Department of Neuroscience and Cell BiologyUniversity of Texas Medical BranchGalvestonUSA

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