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PINCH-2 presents functional copy number variation and suppresses migration of colon cancer cells by paracrine activity

 Chan Hee Park  ;  Sun Young Rha  ;  Joong Bae Ahn  ;  Sang Joon Shin  ;  Woo Sun Kwon  ;  Tae Soo Kim  ;  Sungwhan An  ;  Nam Kyu Kim  ;  Woo-ick Yang  ;  Hyun Cheol Chung 
 INTERNATIONAL JOURNAL OF CANCER, Vol.136(10) : 2273-2283, 2015 
Journal Title
Issue Date
Adaptor Proteins, Signal Transducing/genetics* ; Adaptor Proteins, Signal Transducing/metabolism* ; Cell Line ; Cell Movement ; Colonic Neoplasms/genetics ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology* ; Cytoskeletal Proteins/metabolism ; DNA Copy Number Variations* ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; HCT116 Cells ; Humans ; LIM Domain Proteins/genetics* ; LIM Domain Proteins/metabolism* ; Male ; Membrane Proteins/genetics* ; Membrane Proteins/metabolism* ; Neoplasm Metastasis ; Paracrine Communication* ; Signal Transduction ; Up-Regulation
IPP complex ; PINCH-2 ; Systemic metastasis ; array-CGH ; colon cancer ; copy number variants
In recent years, characterization of cancer and its environment has become necessary. However, studies of the cancer microenvironment remain insufficient. Copy number variations (CNVs) occur in 40% of cancer-related genes, but few studies have reported the correlation between CNVs in morphologically normal tissues adjacent to cancer and cancer progression. In this study, we evaluated cancer cell migration and invasion according to the genetic differences between cancer tissues and their surrounding normal tissues. To study the field cancerization effect, we screened 89 systemic metastasis-related CNVs from morphologically normal tissues adjacent to colon cancers. Among these CNVs, LIM and senescent cell antigen-like domain 2 (PINCH-2) showed copy number amplification and upregulation of mRNA in the nonrelapsed group compared to the systemic relapse group. PINCH-2 expression in colon cancer cells was lower than that in normal epithelial colon cells at both the protein and mRNA levels. Suppression of PINCH-2 resulted in decreased formation of the PINCH-2-IPP (PINCH-2, integrin-linked kinase and α-parvin) complex and reciprocally increased formation of the PINCH-1-IPP complex. Although PINCH-2 expression of survival pathway-related proteins (Akt and phospho-Akt) did not change upon suppression of PINCH-2 expression, cell migration-related proteins [matrix-metalloproteinase (MMP)-9 and -11] were upregulated through autocrine and paracrine activation. Thus, PINCH-2 participates in decreased systemic recurrence by competitively regulating IPP complex formation with PINCH-1, thereby suppressing autocrine and paracrine effects on motility in colon cancer. This genetic change in morphologically normal tissue suggests a field cancerization effect of the tumor microenvironment in cancer progression.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Woo Sun(권우선)
Kim, Nam Kyu(김남규) ORCID logo https://orcid.org/0000-0003-0639-5632
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Park, Chan Hee(박찬희)
Shin, Sang Joon(신상준) ORCID logo https://orcid.org/0000-0001-5350-7241
Ahn, Joong Bae(안중배) ORCID logo https://orcid.org/0000-0001-6787-1503
Yang, Woo Ick(양우익) ORCID logo https://orcid.org/0000-0002-6084-5019
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
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