Differential Expression of CHL1 Gene during Development of Major Human Cancers

Abstract

Background CHL1 gene (also known as CALL) on 3p26.3 encodes a one-pass trans-membrane cell adhesion molecule (CAM). Previously CAMs of this type, including L1, were shown to be involved in cancer growth and metastasis.Methodology/Principal FindingsWe used Clontech Cancer Profiling Arrays (19 different types of cancers, 395 samples) to analyze expression of the CHL1 gene. The results were further validated by RT-qPCR for breast, renal and lung cancer. Cancer Profiling Arrays revealed differential expression of the gene: down-regulation/silencing in a majority of primary tumors and up-regulation associated with invasive/metastatic growth. Frequent down-regulation (>40% of cases) was detected in 11 types of cancer (breast, kidney, rectum, colon, thyroid, stomach, skin, small intestine, bladder, vulva and pancreatic cancer) and frequent up-regulation (>40% of cases) – in 5 types (lung, ovary, uterus, liver and trachea) of cancer. Using real-time quantitative PCR (RT-qPCR) we found that CHL1 expression was decreased in 61% of breast, 60% of lung, 87% of clear cell and 89% papillary renal cancer specimens (P<0.03 for all the cases). There was a higher frequency of CHL1 mRNA decrease in lung squamous cell carcinoma compared to adenocarcinoma (81% vs. 38%, P = 0.02) without association with tumor progression.Conclusions/SignificanceOur results suggested that CHL1 is involved in the development of different human cancers. Initially, during the primary tumor growth CHL1 could act as a putative tumor suppressor and is silenced to facilitate in situ tumor growth for 11 cancer types. We also suggested that re-expression of the gene on the edge of tumor mass might promote local invasive growth and enable further metastatic spread in ovary, colon and breast cancer. Our data also supported the role of CHL1 as a potentially novel specific biomarker in the early pathogenesis of two major histological types of renal cancer.

Integration of High-Resolution Methylome and Transcriptome Analyses to Dissect Epigenomic Changes in Childhood Acute Lymphoblastic Leukemia

“…In pre-B leukemic cells, ETV6-RUNX1 binding to the EPOR promoter was shown to promote cell survival (44). IGF2BP1 is suggested to enhance tumor cell proliferation by sustaining elevated MYC expression (45), TCFL5 downregulation is associated with reduced cell viability of human colorectal cancer cell lines (46), and CHL1 was shown to be differentially expressed during the development of several human cancers (47).…”

Novel tumor suppressor candidates on chromosome 3 revealed by NotI-microarrays in cervical cancer

“…QPCR data were analyzed using the relative quantification or ΔΔC t -method as described. 39 Each reaction was repeated three times. At least 2-fold mRNA changes were considered as significant because of reference genes variability.…”

Molecular features of triple negative breast cancer cells by genome-wide gene expression profiling analysis

“…2, cluster 2 consisted of functions induced by extracellular matrix-cell adhesion-associated genes such as latent transforming growth factor β binding protein 2 (LTBP2), laminin α3 (LAMA3) and cell adhesion molecule with homology to L1CAM (close homolog of L1) (CHL1), which have been reported to be downregulated in various tumors (35)(36)(37). These results suggest that loss of cell -cell or matrix-cell interactions might be a key mechanism in TNBC progression.…”