Tescalcin expression contributes to invasive and metastatic activity in colorectal cancer

Kang, Jieun; Kang, Yun Hee; Oh, Byung Moo; Uhm, Tae Gi; Park, Soo‐Jin; Kim, Tae Woo; Han, Seung Ro; Lee, Seon-Jin; Lee, Younghee; Lee, Hee Gu

doi:10.1007/s13277-016-5262-0

Cited by 23 publications

(16 citation statements)

References 45 publications

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“…BAMBI , a transforming growth factor beta ( TGFB ) inhibitor is up-regulated in metastatic carcinomas including colorectal and osteosarcoma ( Fritzmann et al, 2009 ; Zhou et al, 2013 ). Similarly, the expression of PKP2 , a desmosomal adhesions protein has been implicated in glioma and bladder cancer metastasis ( Takahashi et al, 2012 ; Zhang et al, 2017 ) and high expression of Tescalcin, a gene thought to play a role in cell differentiation and implicated in invasive colorectal cancer ( Kang et al, 2016 ). Furthermore, WNT5B , a gene identified within our scRNA-seq Trailblazers has been implicated in cancer aggressiveness in a number of cancer cell lines and tissues ( Harada et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome analysis of avian neural crest migration reveals signatures of invasion and molecular transitions

Morrison

McLennan

Wolfe

et al. 2017

eLife

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Neural crest cells migrate throughout the embryo, but how cells move in a directed and collective manner has remained unclear. Here, we perform the first single-cell transcriptome analysis of cranial neural crest cell migration at three progressive stages in chick and identify and establish hierarchical relationships between cell position and time-specific transcriptional signatures. We determine a novel transcriptional signature of the most invasive neural crest Trailblazer cells that is consistent during migration and enriched for approximately 900 genes. Knockdown of several Trailblazer genes shows significant but modest changes to total distance migrated. However, in vivo expression analysis by RNAscope and immunohistochemistry reveals some salt and pepper patterns that include strong individual Trailblazer gene expression in cells within other subregions of the migratory stream. These data provide new insights into the molecular diversity and dynamics within a neural crest cell migratory stream that underlie complex directed and collective cell behaviors.

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Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome analysis of avian neural crest migration reveals signatures of invasion and molecular transitions

Morrison

McLennan

Wolfe

et al. 2017

eLife

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“…Recent studies have shown that TESC is involved in the progression of cancer. TESC is overexpressed in colorectal cancer (CRC), but not in normal mucosa and premalignant dysplastic lesions, and its expression contributes to cell proliferation and invasive and metastatic potential 19 , 20 . Furthermore, TESC has been suggested as a potential diagnostic marker for colorectal cancer because serum TESC levels are elevated in patients with CRC.…”

Section: Introductionmentioning

confidence: 99%

Tescalcin/c-Src/IGF1Rβ-mediated STAT3 activation enhances cancer stemness and radioresistant properties through ALDH1

Lee

Choi

Kim

et al. 2018

Sci Rep

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Tescalcin (TESC; also known as calcineurin B homologous protein 3, CHP3) has recently reported as a regulator of cancer progression. Here, we showed that the elevation of TESC in non-small cell lung cancer (NSCLC) intensifies epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties, consequently enhancing the cellular resistance to γ-radiation. TESC expression and the phosphorylation (consequent activation) of signal transducer and activator of transcription 3 (STAT3) were upregulated in CSC-like ALDH1high cells than in ALDH1low cells sorted from A549 NSCLC cells. Knockdown of TESC suppressed CSC-like properties as well as STAT3 activation through inhibition of insulin-like growth factor 1 receptor (IGF1R), a major signaling pathway of lung cancer stem cells. TESC activated IGF1R by the direct recruitment of proto-oncogene tyrosine kinase c-Src (c-Src) to IGF1Rβ complex. Treatment of IGF1R inhibitor, AG1024, also suppressed c-Src activation, implicating that TESC mediates the mutual activation of c-Src and IGF1R. STAT3 activation by TESC/c-Src/IGF1R signaling pathway subsequently upregulated ALDH1 expression, which enhanced EMT-associated CSC-like properties. Chromatin immunoprecipitation and luciferase assay demonstrated that STAT3 is a potential transcription activator of ALDH1 isozymes. Ultimately, targeting TESC can be a potential strategy to overcome therapeutic resistance in NSCLC caused by augmented EMT and self-renewal capacity.

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“…The final classifier used 25 genes (Supplementary Table 5). Notably, 3 of the most informative genes in the classifier ( TESC 10 , SLC6A8 11 , SPP1 12 ) have been implicated in cancer metastasis and another ( E2F1 ) is an established cell proliferation marker. The cross-validated classifier provided excellent separation between CLD and HCC samples, with a preliminary sensitivity of 85% at a specificity of 95% and with identification of both early and late stage HCC (by Milan criteria) (Figure 2D, Supplementary Figure 2).…”

mentioning

confidence: 99%

Detection and Analysis of Circulating Epithelial Cells in Liquid Biopsies From Patients With Liver Disease

et al. 2018

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Epithelial cells in the circulation (circulating epithelial cells, or CECs) are analyzed as a non-invasive method to detect cancers; we investigated whether analysis of hepatocytes in the circulation can identify patients with chronic liver disease or hepatocellular carcinoma (HCC). We previously developed a cell-sorting device to isolate CECs from patient blood samples and combined it with an mRNA analysis system to identify CECs with liver-specific markers. We tested the ability of this device to detect CECs of hepatocyte origin in blood samples from healthy individuals (n=10), patients with chronic liver disease without HCC (n=39), and patients with HCC (n=54), using immunofluorescence. We confirmed hepatocyte origin using RNA-sequencing analysis. We found a similar concentration of circulating hepatocytes in blood samples from patients with chronic liver disease and HCC but an increased concentration from patients with advanced fibrosis compared to those without advanced fibrosis. Circulating hepatocytes isolated from patients with HCC had a different gene expression profile than those from patients with chronic liver disease. This system for detecting and analyzing circulating hepatocytes might be used in the evaluation of benign and malignant liver disease.

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Tescalcin expression contributes to invasive and metastatic activity in colorectal cancer

Cited by 23 publications

References 45 publications

Single-cell transcriptome analysis of avian neural crest migration reveals signatures of invasion and molecular transitions

Single-cell transcriptome analysis of avian neural crest migration reveals signatures of invasion and molecular transitions

Tescalcin/c-Src/IGF1Rβ-mediated STAT3 activation enhances cancer stemness and radioresistant properties through ALDH1

Detection and Analysis of Circulating Epithelial Cells in Liquid Biopsies From Patients With Liver Disease

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