Defects in homologous recombination repair behind the human diseases: FA and HBOC

Katsuki, Yasuji; Takata, Minoru

doi:10.1530/erc-16-0221

Cited by 26 publications

(17 citation statements)

References 172 publications

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“…DSB can be repaired by HR or non-homologous end joining, resulting in cell survival. BRCA2 was the pivotal molecule in HR, and RDA51 was the downstream effector of BRCA2 (Dungl et al 2015, Katsuki & Takata 2016. The present data demonstrated that CDDP induced an increase in the RAD51 protein level in vitro and in vivo (i.e., the signal of DNA damages will initiate repair), which was suppressed in silencing BRCA2.…”

Section: :1supporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

“…The BRCA2 protein directly binds to and regulates the RAD51 protein, an essential molecule for DNA repair via homologous recombination (HR) (Fradet-Turcotte et al 2016, Katsuki & Takata 2016, Yan et al 2016, Sarwar et al 2017. BRCA2-deficient cancer cells are hypersensitive to DNA-crosslinking agents such as cisplatin (CDDP), and therefore BRCA2 may be a target for the management of platinum resistance (Sakai et al 2008, Rytelewski et al 2014, Katsuki & Takata 2016. As to the relationship between the status of BRCA2 and therapeutic outcome of platinum in ovarian cancer, there yet lacks a consensus: BRCA2 mutation is associated with improved sensitivity to platinum and longer survival in certain trials, but other trials have demonstrated that mutation leads to platinum resistance (Liu et al 2012, De Picciotto et al 2016.…”

Section: Introductionmentioning

confidence: 99%

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Knockdown of BRCA2 enhances cisplatin and cisplatin-induced autophagy in ovarian cancer cells

Wan

Dai

Wang

et al. 2018

Endocrine-Related Cancer

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Clinical implications of the BRCA2 expression level on treatments of ovarian cancer are controversial. Here, we demonstrated that platinum-resistant cancer had a higher percentage of high BRCA2 level (87.5% vs 43.6%, = 0.001), and that patients with a low BRCA2 level in cancer tissues had longer progression-free survival (with a median time of 28.0 vs 12.0 months, < 0.001) and platinum-free duration (with a median time of 19.0 vs 5.0 months, < 0.001) compared with those with a high BRCA2 level. In human ovarian cancer cell lines CAOV-3 and ES-2, cisplatin induced an upregulation of the RAD51 protein, which was inhibited after silencing ; silencing enhanced the action of cisplatin and Knockdown of BRCA2 promoted cisplatin-induced autophagy. Interestingly, the autophagy blocker chloroquine enhanced cisplatin in BRCA2-silenced cells accompanied by an increase in apoptotic cells, which did not occur in BRCA2-intact cells; chloroquine enhanced the efficacy of cisplatin against BRCA2-silenced CAOV-3 tumors , with an increase in LC3-II level in tumor tissues. Sensitization of cisplatin was also observed in BRCA2-silenced CAOV-3 cells after inhibiting ATG7, confirming that chloroquine modulated the sensitivity via the autophagy pathway. These data suggest that a low BRCA2 level can predict better platinum sensitivity and prognosis, and that the modulation of autophagy can be a chemosensitizer for certain cancers.

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Section: :1supporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Knockdown of BRCA2 enhances cisplatin and cisplatin-induced autophagy in ovarian cancer cells

Wan

Dai

Wang

et al. 2018

Endocrine-Related Cancer

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“…In the review by Katsuki and Takata (Katsuki & Takata 2016), the connection between the Fanconi Anemia (FA) pathway and susceptibility to breast and ovarian cancer is discussed in depth. The authors first describe the clinical connections between FA and hereditary breast and ovarian cancer (HBOC) and then cover some of the same terrain reviewed by Orthwein and coworkers, but with a much greater focus on the key function of FA proteins: interstrand crosslink repair (ICL).…”

mentioning

confidence: 99%

BRCA2: a grown-up cancer susceptibility gene

Foulkes

Sugano

2016

Endocrine-Related Cancer

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“…3,4 The FA protein family consists of 15 members that regulate cell cycle progression and DNA damage repair. 5 Several studies have investigated the role of FA proteins in the occurrence and development of cancer. For example, Yao et al showed that FANCF (HGNC ID: 3587; UniProt ID: Q9NPI8) plays a key role in the drug resistance of leukemia cells via regulation of DNA repair, 6 while Park et al showed that deficiency of FANCD2 (HGNC ID: 3585, UniProt ID: Q9BXW9) leads to skin cancer.…”

Section: Introductionmentioning

confidence: 99%

<p>FANCI Cooperates with IMPDH2 to Promote Lung Adenocarcinoma Tumor Growth via a MEK/ERK/MMPs Pathway</p>

Zheng¹,

Li²

2020

OTT

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Purpose: Fanconi anemia complementation group I (FANCI) is a key protein in ribosome biogenesis and DNA repair. Here, we aimed to determine the clinical significance, prognostic value and biology functions of FANCI in lung adenocarcinoma (LUAD). Methods: The expression of FANCI in LUAD tissue and its relationship with patient outcomes were assessed using bioinformatics analysis, as well as quantitative reverse-transcription PCR (qRT-PCR) and Western blot analysis of LUAD tissue and adjacent normal lung tissue. The chisquared test and Cox regression analysis were used to analyze the clinical significance of FANCI expression. The biological effects of FANCI knockdown in human LUAD cell lines were investigated by analysis of proliferation, colony formation, cell cycle distribution, migration, and invasion in vitro, and monitoring of tumor xenograft growth in vivo. FANCI interactions with IMPDH2 and involvement in MEK/ERK/MMPs signaling were analyzed using coimmunoprecipitation assays, immunofluorescence microscopy, and Western blotting. Results: FANCI was identified as a hub gene for LUAD. FANCI expression was upregulated in LUAD tissues compared with normal lung tissues and was positively associated with lymphatic metastasis, distant metastasis, and poor outcome. FANCI was also an independent prognostic factor in LUAD patients. Knockdown of FANCI in LUAD cell lines decreased their proliferation, migration, invasion, and cell cycle progression in vitro, and decreased the growth of xenografts in mice. Direct binding of FANCI to IMPDH2 decreased IMPDH2 degradation, regulated activation of MEK/ERK/MMPs signaling. Overexpression of IMPDH2 reversed the inhibitory effects of FANCI knockdown. Conclusion: FANCI may act as an oncogene in LUAD by cooperating with IMPDH2 to promote cell proliferation via the MEK/ERK/MMPs pathway. These results identify FANCI as a potential prognostic biomarker and therapeutic target for LUAD.

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Defects in homologous recombination repair behind the human diseases: FA and HBOC

Cited by 26 publications

References 172 publications

Knockdown of BRCA2 enhances cisplatin and cisplatin-induced autophagy in ovarian cancer cells

Knockdown of BRCA2 enhances cisplatin and cisplatin-induced autophagy in ovarian cancer cells

BRCA2: a grown-up cancer susceptibility gene

<p>FANCI Cooperates with IMPDH2 to Promote Lung Adenocarcinoma Tumor Growth via a MEK/ERK/MMPs Pathway</p>

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