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PINCH‐2 presents functional copy number variation and suppresses migration of colon cancer cells by paracrine activity
Author(s) -
Park Chan Hee,
Rha Sun Young,
Ahn Joong Bae,
Shin Sang Joon,
Kwon Woo Sun,
Kim Tae Soo,
An Sungwhan,
Kim Nam Kyu,
Yang Wooick,
Chung Hyun Cheol
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29273
Subject(s) - autocrine signalling , paracrine signalling , biology , colorectal cancer , cancer research , cancer , cancer cell , cell migration , metastasis , cell , genetics , cell culture , receptor
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.