Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance

Chiou, Shin Heng; Dorsch, Madeleine; Kusch, Eva; Naranjo, Santiago; Kozak, Margaret M.; Koong, Albert C.; Winslow, Monte M.; Grüner, Barbara M.

doi:10.1038/s41598-018-32159-x

Cited by 29 publications

(24 citation statements)

References 60 publications

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“…The DPI‐ELISA enables analysis of DNA‐protein interactions in multiple samples in a single run (Figure 1). Using the DPI‐ELISA method, Alonso et al 49 identified netropsin as a specific inhibitor of mammalian high‐mobility group protein AT‐hook 2 (HMGA2), which is associated with metastasis in several types of cancers 55‐57 …”

Section: Development Of High‐throughput Screening Methodsmentioning

confidence: 99%

Targeting DNA binding proteins for cancer therapy

et al. 2020

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Yoshitomo Shiroma and Ryou-u Takahashi contributed equally to this work.Abbreviations: AEP, AF4 family/ENL family/P-TEFb; ARNT, aryl hydrocarbon receptor nuclear translocator; BRD4, bromodomain-containing protein 4; CBP, CREB-binding protein; DUX4, double homeobox protein 4; ETO, eight-twenty one; EWS, Ewing's sarcoma; FLI1, friend leukemia virus integration 1; HIF, hypoxia-inducible factor; MLL, mixed-lineage leukemia; SOX2, Sry-related high-mobility box 2; STAT3, signal transducer and activator of transcription 3; TF, transcription factor; TRF, telomere-repeat binding factor. AbstractDysregulation or mutation of DNA binding proteins such as transcription factors (TFs) is associated with the onset and progression of various types of disease, including cancer. Alteration of TF activity occurs in numerous cancer tissues due to gene amplification, deletion, and point mutations, and epigenetic modification. Although cancer-associated TFs are promising targets for cancer therapy, development of drugs targeting these TFs has historically been difficult due to the lack of high-throughput screening methods. Recent advances in technology for identification and selective inhibition of DNA binding proteins enable cancer researchers to develop novel therapeutics targeting cancer-associated TFs. In the present review, we summarize known cancer-associated TFs according to cancer type and introduce recently developed high-throughput approaches to identify selective inhibitors of cancer-associated TFs. K E Y W O R D SDNA binding protein, drug discovery, high-throughput screening, telomere, transcription factor | 1059 SHIROMA et Al.

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Section: Development Of High‐throughput Screening Methodsmentioning

confidence: 99%

Targeting DNA binding proteins for cancer therapy

et al. 2020

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“…In addition to the prevalent view that HMGA2 is a proto‐oncogene whose activation plays a major role in malignant transformation, [ 20 ] there is emerging evidence that HMGA2 is functionally dispensable for in vivo malignant transformation and progression of skin or pancreatic cancers based on studies in mouse models. [ 15,21 ] Despite the ubiquitous upregulation of HMGA2 in human SCC tumors and cells, we found that short‐term UVR decreased HMGA2 expression in vitro in cultured human keratinocytes and SCC cells (Figure 1E,F). In contrast, long‐term chronic UVR augmented Hmga2 expression in mouse epidermis (Figure 2B,D).…”

Section: Discussionmentioning

confidence: 91%

Biomarker function of HMGA2 in ultraviolet‐induced skin cancer development

Hinde

Xie

et al. 2020

Experimental Dermatology

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The high mobility group AT‐hook 2 (HMGA2) gene encodes a transcription factor that is expressed during embryonic development but down‐regulated in adult tissues. Its re‐expression in adult tissues is often associated with tumorigenesis. In this study, we found that HMGA2 is highly expressed in human cutaneous squamous cell carcinoma (SCC) cell lines and primary SCC tumors, but not in adjacent normal skin. In non‐ultraviolet (UV)‐irradiated mouse skin, baseline Hmga2 expression was detected in the epidermis but not in hair follicles. Following chronic UV exposure, we found activation of Hmga2 in hair follicles. UV‐induced mouse skin SCC tumors displayed a ubiquitous increase in Hmga2 expression compared to non‐tumor‐bearing adjacent skin. In human SCC cells, decreased HMGA2 expression was linked with reduced cell proliferation following depletion of FOXM1 and TRIP13, two UV master regulator genes. Taken together, these findings highlight an important biomarker function of HMGA2 expression in UV‐induced skin tumorigenesis and cell proliferation.

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“…HMGA2 was previously reported to be involved in the regulation of cellular behavior in several types of human cancer (15–18). In addition, HMGA2 was recently identified to be dispensable for pancreatic cancer progression, metastasis and therapy resistance (26). Hawsawi et al (27) revealed that HMGA2 may promote epithelial-mesenchymal transition of prostate cancer via the mitogen-activated protein kinase pathway.…”

Section: Discussionmentioning

confidence: 99%

miR‑490‑3p functions as a tumor suppressor in glioma by inhibiting high‑mobility group AT‑hook 2 expression

Zhang

Wang

et al. 2019

Exp Ther Med

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Glioma is one of the most common types of malignant cancer and the significance of microRNAs (miRNAs) in cancer therapy has been demonstrated. In the current study, miR-490-3p expression was significantly downregulated in glioma tissue and cell lines. Overexpression of miR-490-3p inhibited glioma cell proliferation and migration in vitro . In addition, the high-mobility group AT-hook 2 (HMGA2) was identified as a candidate target gene of miR-490-3p. The current study demonstrated that miR-490-3p mimic could inhibit HMGA2 protein expression in glioma cells. In addition, correlation analysis demonstrated that miR-490-3p and HMGA2 expression was inversely correlated in glioma tissues. Furthermore, the inhibitory effect of miR-490-3p mimic on cell proliferation and migration was partially reversed by the overexpression of HMGA2. Taken together, these results suggest that miR-490-3p may have a tumor suppressive role in glioma and therefore miR-490-3p may be a new target for the treatment of glioma.

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Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance

Cited by 29 publications

References 60 publications

Targeting DNA binding proteins for cancer therapy

Targeting DNA binding proteins for cancer therapy

Biomarker function of HMGA2 in ultraviolet‐induced skin cancer development

miR‑490‑3p functions as a tumor suppressor in glioma by inhibiting high‑mobility group AT‑hook 2 expression

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