CCN6 regulates IGF2BP2 and HMGA2 signaling in metaplastic carcinomas of the breast

McMullen, Emily R; González, María E.; Skala, Stephanie L.; Tran, Mai; Thomas, Dafydd G.; Djomehri, Sabra; Burman, Boris; Kidwell, Kelley M.; Kleer, Celina G.

doi:10.1007/s10549-018-4960-2

Cited by 24 publications

(30 citation statements)

References 36 publications

(64 reference statements)

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“…We found a high expression of IGF2BP2 in HNSCC tumor tissues and verified this result in our laboratory using immunohistochemistry. This is consistent with previous studies of IGF2BP2 in cancers, including colorectal cancer (Wang et al, 2019), gastrointestinal cancer (Zhou et al, 2017), endometrial cancer (Hiramatsu et al, 2016), pancreas cancer (Xu et al, 2019), breast cancer (McMullen et al, 2018), and hepatic carcinoma. We found that the upregulation of IGF2BP2 had some statistical correlation with the T stage, HPV status, and overall survival in HNSCC.…”

Section: Discussionsupporting

confidence: 93%

Clinical Significance of an m6A Reader Gene, IGF2BP2, in Head and Neck Squamous Cell Carcinoma

Duan

Jiang

Liu

et al. 2020

Front. Mol. Biosci.

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The importance of N6-methyladenosine (m6A) in tumor recurrence and prognosis has been recognized in recent years. The role of m6A readers, such as insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), in regulating head and neck squamous cell carcinoma (HNSCC) remains unclear. We, therefore, assessed the prognostic role of IGF2BP2 in HNSCC using openly available data from The Cancer Genome Atlas (TCGA) in conjunction with HNSCC patient sample immunohistochemistry (n = 36). The correlation between IGF2BP2 expression and clinical characteristics was then examined. The role of IGF2BP2 in prognosis was assessed by Kaplan-Meier curves and Cox analysis. Finally, TCGA data was used to explore possible carcinogenic mechanisms with multi-GSEA (gene set enrichment analysis). Analysis of TCGA data and IHC results revealed that IGF2BP2 was upregulated in HNSCC tumor tissues, and the expression level was related to the T stage. Simultaneously, Kaplan-Meier curves and Cox analysis indicated that highly expressed IGF2BP2 correlated with poor prognosis and that IGF2BP2 was a potential prognostic factor for HNSCC. Gene set enrichment analysis revealed that scavenging and degradation, synthesis and metabolism, cell growth, death and motility, and cancer pathways were differentially enriched in patients with high IGF2BP2 expression. Our results demonstrate that IGF2BP2 plays an important role in tumor progression and may serve as an important biological prognostic factor for HNSCC. Keywords: head and neck squamous cell carcinoma (HNSCC), insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), N6-methyladenosine (m6A), prognostic factor, tumor

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Section: Discussionsupporting

confidence: 93%

Clinical Significance of an m6A Reader Gene, IGF2BP2, in Head and Neck Squamous Cell Carcinoma

Duan

Jiang

Liu

et al. 2020

Front. Mol. Biosci.

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“…Meanwhile, Ccn6, secreted by normal breast epithelium, can suppress the expression of IGF2BP2 protein in cancerous breast tissues, thus modulating the growth of the tumor. Ccn6/Wisp3 knockdown up-regulated the expression of IGF2BP2 in mice, who developed mammary carcinomas characterized by spindle and squamous differentiation, validated hallmarks of metaplastic breast carcinomas [ 74 ] (Fig. 3 ).…”

Section: Igf2bp2 and Cancersmentioning

confidence: 99%

The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

2021

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The human insulin-like growth factor 2 (IGF2) mRNA binding proteins 2 (IGF2BP2/IMP2) is an RNA-binding protein that regulates multiple biological processes. Previously, IGF2BP2 was thought to be a type 2 diabetes (T2D)-associated gene. Indeed IGF2BP2 modulates cellular metabolism in human metabolic diseases such as diabetes, obesity and fatty liver through post-transcriptional regulation of numerous genes in multiple cell types. Emerging evidence shows that IGF2BP2 is an N6-methyladenosine (m6A) reader that participates in the development and progression of cancers by communicating with different RNAs such as microRNAs (miRNAs), messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs). Additionally, IGF2BP2 is an independent prognostic factor for multiple cancer types. In this review, we summarize the current knowledge on IGF2BP2 with regard to diverse human metabolic diseases and its potential for cancer prognosis.

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“…Collectively, these studies suggest that CCN6, IGF2BP2, and HMGA2 signaling pathway may play a functional role in the development of spindle and squamous metaplastic carcinomas, with promise as biomarkers and potential targets. 44…”

Section: New Promising Molecular Alterations In Metaplastic Carcinommentioning

confidence: 99%

Metaplastic Breast Carcinoma: Update on Histopathology and Molecular Alterations

McMullen

Zoumberos

Kleer

2019

Archives of Pathology &Amp; Laboratory Medicine

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Context— Metaplastic carcinoma is a rare, triple-negative carcinoma of the breast that exhibits transformation of part or all of its glandular carcinomatous component into a nonglandular, or metaplastic, component. The World Health Organization currently recognizes 5 variants of metaplastic carcinoma based on their histologic appearance. Objective— To review the histologic classifications, differential diagnosis, prognosis, and recent laboratory studies of metaplastic breast carcinoma. Data Sources.— We reviewed recently published studies that collectively examine metaplastic carcinomas, including results from our own research. Conclusions.— Metaplastic breast carcinoma has a broad spectrum of histologic patterns, often leading to a broad differential diagnosis. Diagnosis can typically be rendered by a combination of morphology and immunohistochemical staining for high-molecular-weight cytokeratins and p63. Recent studies elucidate new genes and pathways involved in the pathogenesis of metaplastic carcinoma, including the downregulation of CCN6 and WNT pathway gene mutations, and provide a novel MMTV-Cre; Ccn6fl/fl knockout disease-relevant mouse model to test new therapies.

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CCN6 regulates IGF2BP2 and HMGA2 signaling in metaplastic carcinomas of the breast

Abstract: These data shed light into the pathogenesis of metaplastic carcinoma and demonstrate a novel CCN6/IGF2BP2/HMGA2 oncogenic pathway with biomarker and therapeutic implications.

Cited by 24 publications

References 36 publications

Clinical Significance of an m6A Reader Gene, IGF2BP2, in Head and Neck Squamous Cell Carcinoma

Clinical Significance of an m6A Reader Gene, IGF2BP2, in Head and Neck Squamous Cell Carcinoma

The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

Metaplastic Breast Carcinoma: Update on Histopathology and Molecular Alterations

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