Serum deprivation‐response protein regulates aldehyde dehydrogenase 1 through integrin‐linked kinase signaling in endometrioid carcinoma cells

Tahara, Shinichiro; Nojima, Satoshi; Ohshima, Kenji; Hori, Yumiko; Kurashige, Masako; Wada, Naoki; Motoyama, Yuichi; Okuzaki, Daisuke; Ikeda, Jun‐ichiro; Morii, Eiichi

doi:10.1111/cas.14007

Cited by 12 publications

(17 citation statements)

References 27 publications

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“…CRISPR technology was used to show that serum deprivation-response protein affects the expression of ALDH1 in HEC1B, HEC-108, HEC-116, and SNG-M cells. These studies essentially represent endometrioid carcinomas [118]. In serous carcinoma cell lines, CRISPR technology was used to introduce mutations in FBXW7 , F-box, and WD repeat domain containing 7.…”

Section: Model Systemsmentioning

confidence: 99%

Unique Molecular Features in High-Risk Histology Endometrial Cancers

Pandita

Wang

Jones

et al. 2019

Cancers

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Endometrial cancer is the most common gynecologic malignancy in the United States and the sixth most common cancer in women worldwide. Fortunately, most women who develop endometrial cancer have low-grade early-stage endometrioid carcinomas, and simple hysterectomy is curative. Unfortunately, 15% of women with endometrial cancer will develop high-risk histologic tumors including uterine carcinosarcoma or high-grade endometrioid, clear cell, or serous carcinomas. These high-risk histologic tumors account for more than 50% of deaths from this disease. In this review, we will highlight the biologic differences between low- and high-risk carcinomas with a focus on the cell of origin, early precursor lesions including atrophic and proliferative endometrium, and the potential role of stem cells. We will discuss treatment, including standard of care therapy, hormonal therapy, and precision medicine-based or targeted molecular therapies. We will also discuss the impact and need for model systems. The molecular underpinnings behind this high death to incidence ratio are important to understand and improve outcomes.

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Section: Model Systemsmentioning

confidence: 99%

Unique Molecular Features in High-Risk Histology Endometrial Cancers

Pandita

Wang

Jones

et al. 2019

Cancers

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“…We found that NNMT is related to MELF pattern invasion of EC and that depletion of NNMT markedly attenuates the migration and invasion of EC cells. Previously, we reported that high S100A4 and SDPR expression in EC are related to MELF pattern invasion and showed the genetic characteristics of EC with MELF invasion 3,4 . However, we did not explore what contributed to the characteristic morphology in invasive front area of MELF.…”

Section: Discussionmentioning

confidence: 85%

Nicotinamide N‐methyltransferase is related to MELF pattern invasion in endometrioid carcinoma

et al. 2021

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Grade 1 (G1) endometrioid carcinoma (EC) is relatively a good prognosis. However, in a minority of cases, G1 shows an aggressive histological pattern known as the microcystic, elongated, and fragmented (MELF) pattern. We previously reported that EC with high expression levels of S100A4 and serum deprivation‐response protein (SDPR) was related to MELF pattern invasion. However, the molecular features of the invasive front area of the MELF pattern have not been investigated. In this study, we searched for genes preferentially expressed in the invasive front area of EC with the MELF pattern using laser microdissection and RNA sequencing, and showed that nicotinamide N‐methyltransferase (NNMT) is related to MELF pattern invasiveness. Immunohistochemical analyses confirmed high NNMT expression in the invasive front area of the MELF pattern. Moreover, NNMT promoted migration, invasion, colony formation, epithelial–mesenchymal transition (EMT), and chemoresistance using EC cell lines. We speculate that depletion of NNMT promotes histone methylation and leads to tumor suppression because NNMT consumes S‐adenosyl methionine (SAM), which is an essential methylation cofactor. NNMT knockout cells showed enhanced expression of H3K9me2. RNA sequencing using NNMT knockout cell lines suggested that methylation of H3K9 leads to repression of the transcription of various oncogenic genes. Our findings demonstrate the possibility that NNMT inhibitors, which are expected to be used for the treatment of metabolic disorders, would be effective for the treatment of aggressive EC. This is the first report of gene analyses focusing on the morphological changes associated with MELF pattern invasion of EC.

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“…Pathological changes in these genes can cause anomalistic transduction of signal pathways such as AKT‐/‐PI3K, NF‐κB, MARK, and Wnt‐/‐β‐catenin, or abnormal expression of P53 and P16 proteins, leading to uncontrolled cell proliferation and tumorigenesis. Given its extensive study in tumors and obvious therapeutic effect, the CRISPR‐Cas9 technology has been used in related research and treatment of endometrial cancer (summarized in Table ).…”

Section: Endometrial Cancer and Crispr‐cas9mentioning

confidence: 99%

“…Knockout of S100A4 in the endometrial cancer cell line, HEC‐1B, by the CRISPR‐Cas9 technology, inhibits AKT phosphorylation and activation of MMP2, leading to reduced proliferation and invasion of HEC‐1B cells . SDPR gene depletion by CRISPR‐Cas9 in HEC‐1B and HEC‐108 cells can suppress tumor cell migration, invasion and EMT by inhibiting the ILK‐/‐ALDH1 pathway . Knockout of MIR‐203 in RUCA‐1 cells caused tumor cells to stagnate in the G2 phase of the cell cycle and cell viability also decreased .…”

Section: Endometrial Cancer and Crispr‐cas9mentioning

confidence: 99%

Applications of CRISPR‐Cas9 in gynecological cancer research

et al. 2020

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Gynecological cancers pose a significant threat to women's health worldwide, with cervical cancer, ovarian cancer, and endometrial cancer having high incidences.Current gynecological cancer treatment methods mainly include surgery, chemotherapy, radiotherapy, and chemoradiotherapy. The CRISPR-Cas9 gene editing technology as a new therapeutic method has shown tremendous effect in the treatment of other cancers, promoting research on its potential therapeutic effect in gynecological cancer. In this article, we reviewed the current research status of CRISPR-Cas9 technology in gynecological cancer, focusing on the importance of studying the mechanism of CRISPR-Cas9 in gynecological cancer treatment, thereby laying a foundation for further research on its clinical application. K E Y W O R D S cancer treatment, CRISPR-Cas9, gene editing, gynecological cancers 1 | INTRODUCTIONThe CRISPR sequence, a cluster of regularly spaced short palindromic repeats, is a special ordered repeating sequence found in the genome of Escherichia coli. The CRISPR-Cas9 system constitutes the acquired immune system of E. coli. 1 In 2012, scientists discovered that the CRISPR-Cas9 system can produce mature CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA), which form a composite structure and have a directional guidance function to guide Cas9 to specific DNA sequences, resulting in DNA double-strand breaks. 2 By 2013, scientists had successfully edited the genome of eukaryotic cells using the CRISPR-Cas9 system. [3][4][5] Since then, the CRISPR-Cas9 gene editing technology has dramatically impacted the field of life sciences and has become one of the most significant research areas at present. The working principle of the CRISPR-Cas9 system is to artificially design two kinds of RNA: crRNA and tracrRNA, and then transform them into a single guide RNA (sgRNA), thereby guiding Cas9 to cut DNA in a targeted manner, following which cells are able to delete the target DNA through homologous and non-homologous DNA damage repair mechanisms. 6 Compared with traditional gene editing tools, such as ZFN and TALEN, the CRISPR-Cas9 technology has the advantages of simple design, ability to target any DNA sequence in the cell and to target multiple targets simultaneously, higher cutting efficiency, and lower cost. 7 At present, the CRISPR-Cas9 gene editing technology has contributed to great advancements in the clinical treatment of diseases. Major breakthroughs have been achieved in treating hereditary diseases using this technology. [8][9][10] It was used to knock out the beta-globin gene, the pathogenic gene of β-hemoglobinopathy, and it also employed rAAV6, as a donor template, to effectively correct the disease-causing mutation of SCD through homologous recombination. 10 In addition, The CRISPR-Cas9 gene editing technology has been widely used treatment-related researches and in the establishment of disease model of many cancers, including pancreatic, lung, gastric, colon, kidney, liver, head and neck, and skin cancers. [11][12][13][14][15][16][...

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Serum deprivation‐response protein regulates aldehyde dehydrogenase 1 through integrin‐linked kinase signaling in endometrioid carcinoma cells

Cited by 12 publications

References 27 publications

Unique Molecular Features in High-Risk Histology Endometrial Cancers

Unique Molecular Features in High-Risk Histology Endometrial Cancers

Nicotinamide N‐methyltransferase is related to MELF pattern invasion in endometrioid carcinoma

Applications of CRISPR‐Cas9 in gynecological cancer research

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