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

Chan Hee Park, SunYoung Rha, Joong Bae Ahn, Sang Joon Shin, Woo Sun Kwon, Tae Soo Kim, Sungwhan An, Namkyu Kim, Woo Ick Yang, Hyuncheol Chung

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2273-2283
Number of pages11
JournalInternational Journal of Cancer
Volume136
Issue number10
DOIs
Publication statusPublished - 2015 May 15

Fingerprint

Colonic Neoplasms
Neoplasms
Tumor Microenvironment
Cell Movement
Matrix Metalloproteinase 11
Recurrence
Messenger RNA
Proteins
Neoplasm Genes
Matrix Metalloproteinase 9
Colon
Up-Regulation
Epithelial Cells
Neoplasm Metastasis
Antigens
indolepropanol phosphate

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Park, Chan Hee ; Rha, SunYoung ; Ahn, Joong Bae ; Shin, Sang Joon ; Kwon, Woo Sun ; Kim, Tae Soo ; An, Sungwhan ; Kim, Namkyu ; Yang, Woo Ick ; Chung, Hyuncheol. / PINCH-2 presents functional copy number variation and suppresses migration of colon cancer cells by paracrine activity. In: International Journal of Cancer. 2015 ; Vol. 136, No. 10. pp. 2273-2283.
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abstract = "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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PINCH-2 presents functional copy number variation and suppresses migration of colon cancer cells by paracrine activity. / Park, Chan Hee; Rha, SunYoung; Ahn, Joong Bae; Shin, Sang Joon; Kwon, Woo Sun; Kim, Tae Soo; An, Sungwhan; Kim, Namkyu; Yang, Woo Ick; Chung, Hyuncheol.

In: International Journal of Cancer, Vol. 136, No. 10, 15.05.2015, p. 2273-2283.

Research output: Contribution to journalArticle

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T1 - PINCH-2 presents functional copy number variation and suppresses migration of colon cancer cells by paracrine activity

AU - Park, Chan Hee

AU - Rha, SunYoung

AU - Ahn, Joong Bae

AU - Shin, Sang Joon

AU - Kwon, Woo Sun

AU - Kim, Tae Soo

AU - An, Sungwhan

AU - Kim, Namkyu

AU - Yang, Woo Ick

AU - Chung, Hyuncheol

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AB - 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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