Dataset Information

Establishment and Characterization of Paired Primary and Peritoneal Seeding Human Colorectal Cancer Cell Lines: Identification of Genes That Mediate Metastatic Potential.

ABSTRACT: Peritoneal metastasis is one of the major patterns of unresectability in colorectal cancer (CRC) and a cause of death in advanced CRC. Identification of distinct gene expressions between primary CRC and peritoneal seeding metastasis is to predict the metastatic potential of primary human CRC. Three pairs of primary CRC (SNU-2335A, SNU-2404A, and SNU-2414A) and corresponding peritoneal seeding (SNU-2335D, SNU-2404B, and SNU-2414B) cell lines were established to determine the different gene expressions and resulting aberrated signaling pathways in peritoneal metastasis tumor using whole exome sequencing and microarray. Whole exome sequencing detected that mutation in CYP2A7 was exclusively shared in peritoneal seeding cell lines. Microarray identified that there were five upregulated genes (CNN3, SORBS1, BST2, EPSTI1, and KLHL5) and two downregulated genes (TRY6 and STYL5) in the peritoneal metastatic cell lines. CNN3 expression was highly augmented in both mRNA and protein levels in peritoneal metastasis cells. Knockdown of Calponin 3 resulted in augmented level of E-cadherin in peritoneal metastasis cells, and migration and invasiveness decreased accordingly. We suggest that CNN3 takes part in cell projection and movement, and the detection and distribution of CNN3 may render prognostic information for predicting peritoneal seeding metastasis from primary colorectal cancer.

SUBMITTER: Kim SC

PROVIDER: S-EPMC6097464 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Establishment and Characterization of Paired Primary and Peritoneal Seeding Human Colorectal Cancer Cell Lines: Identification of Genes That Mediate Metastatic Potential.

Kim Soon-Chan SC Hong Chang-Won CW Jang Sang-Geun SG Kim Ye-Ah YA Yoo Byong-Chul BC Shin Young-Kyoung YK Jeong Seung-Yong SY Ku Ja-Lok JL Park Jae-Gahb JG

Translational oncology 20180814 5

Peritoneal metastasis is one of the major patterns of unresectability in colorectal cancer (CRC) and a cause of death in advanced CRC. Identification of distinct gene expressions between primary CRC and peritoneal seeding metastasis is to predict the metastatic potential of primary human CRC. Three pairs of primary CRC (SNU-2335A, SNU-2404A, and SNU-2414A) and corresponding peritoneal seeding (SNU-2335D, SNU-2404B, and SNU-2414B) cell lines were established to determine the different gene expres ...[more]

PMID: 30114595

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Project description:Colorectal cancer (CRC) is one of the major causes of cancer deaths across the world. Patients' survival at time of diagnosis depends mainly on stage of the tumor. Therefore, understanding the molecular mechanisms from low-grade to high-grade stages of cancer that lead to cellular migration from one tissue/organ to another tissue/organ is essential for implementing therapeutic approaches. To this end, we performed a unique meta-analysis flowchart by identifying differentially expressed genes (DEGs) between normal, primary (primary sites), and metastatic samples (Colorectal metastatic lesions in liver and lung) in some Test datasets. DEGs were employed to construct a protein-protein interaction (PPI) network. A smaller network containing 39 DEGs was then extracted from the PPI network whose nodes expression induction or suppression alone or in combination with each other would inhibit tumor progression or metastasis. These DEGs were then verified by gene expression profiling, survival analysis, and multiple Validation datasets. We suggested for the first time that downregulation of mitochondrial genes, including ETHE1, SQOR, TST, and GPX3, would help colorectal cancer cells to produce more energy under hypoxic conditions through mechanisms that are different from "Warburg Effect". Augmentation of given antioxidants and repression of P4HA1 and COL1A2 genes could be a choice of CRC treatment. Moreover, promoting active GSK-3β together with expression control of EIF2B would prevent EMT. We also proposed that OAS1 expression enhancement can induce the anti-cancer effects of interferon-gamma, while suppression of CTSH hinders formation of focal adhesions. ATF5 expression suppression sensitizes cancer cells to anchorage-dependent death signals, while LGALS4 induction recovers cell-cell junctions. These inhibitions and inductions would be another combinatory mechanism that inhibits EMT and cell migration. Furthermore, expression inhibition of TMPO, TOP2A, RFC3, GINS1, and CKS2 genes could prevent tumor growth. Besides, TRIB3 suppression would be a promising target for anti-angiogenic therapy. SORD is a poorly studied enzyme in cancer, found to be upregulated in CRC. Finally, TMEM131 and DARS genes were identified in this study whose roles have never been interrogated in any kind of cancer, neither as a biomarker nor curative target. All the mentioned mechanisms must be further validated by experimental wet-lab techniques.

Dataset Information

Establishment and Characterization of Paired Primary and Peritoneal Seeding Human Colorectal Cancer Cell Lines: Identification of Genes That Mediate Metastatic Potential.

Publications

Establishment and Characterization of Paired Primary and Peritoneal Seeding Human Colorectal Cancer Cell Lines: Identification of Genes That Mediate Metastatic Potential.

Similar Datasets

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