CK2α/CSNK2A1 Phosphorylates SIRT6 and Is Involved in the Progression of Breast Carcinoma and Predicts Shorter Survival of Diagnosed Patients

Bae, Jong Seok; Park, See‐Hyoung; Jamiyandorj, Urangoo; Kim, Kyoung Min; Noh, Sang Jae; Kim, Jung Ryul; Park, Hye Jeong; Kwon, Keun Sang; Jung, Sung Hoo; Park, Ho Sung; Park, Byung‐Hyun; Lee, Ho; Moon, Woo Sung; Sylvester, Karl G.; Jang, Kyu Yun

doi:10.1016/j.ajpath.2016.08.007

Cited by 73 publications

(130 citation statements)

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“…The sum score ranged from zero to eight. Subsequently, sum scores of the nuclear and cytoplasmic expression of FAM83H were grouped as positive or negative by receiver operating characteristic curve analysis at the highest positive likelihood ratio point for the estimation of death of HCC patients 42, 43 .…”

Section: Methodsmentioning

confidence: 99%

FAM83H is involved in the progression of hepatocellular carcinoma and is regulated by MYC

Kim

Park

Bae

et al. 2017

Sci Rep

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Family with sequence similarity 83, member h (FAM83H) was identified, from a genome-wide search, as having the genetic etiology of human autosomal dominant hypocalcified amelogenesis imperfecta 1 . Thereafter, various mutations of FAM83H have been detected in amelogenesis imperfecta 1-5 and FAM83H-associated amelogenesis imperfecta is reported to be the most prevalent form of amelogenesis imperfecta 3,6 . Therefore, studies on FAM83H have typically been focused on tooth development. However, the cytoplasmic localization of FAM83H protein suggests that FAM83H might be involved in other cellular processes, including tumorigenesis 2, 5 . Increased expression of FAM83H in cancer tissue compared with normal tissue has been presented in recent microarray data 7 . In colorectal cancer, FAM83H contributes to the progression of cancer via regulating keratin cytoskeleton organization [8][9][10] . FAM83H overexpression along with aberrant localization of CK-1α could contribute to the progression of colorectal cancer through keratin cytoskeleton organization 8 . Another study showed that FAM83H could be an important molecule that can cause androgen independent prostate cancer progression 11 .

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Section: Methodsmentioning

confidence: 99%

FAM83H is involved in the progression of hepatocellular carcinoma and is regulated by MYC

Kim

Park

Bae

et al. 2017

Sci Rep

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“…(6) CKA2 , the alpha catalytic subunit of casein kinase 2, has two human homologs, CSNK2A1 and CSNK2A2, which were OES with gemcitabine. They can be upregulated in cancer [186-191] and are considered targets for treatment [193]; (7) CLB2/CCNA2/CCNB1, a B-type cyclin involved in cell cycle progression, of which both CCNA2 and CCNB1 are overexpressed in breast and colorectal cancer [194-197]. Moreover, the observation that CLB2 deletion (suppressing effect) opposes that of CLB5 (deletion enhancing; see above Fig.…”

Section: Resultsmentioning

confidence: 99%

A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity

Santos

Icyuz

Pound

et al. 2019

Preprint

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10Knowledge about synthetic lethality can be applied to enhance the efficacy of 11 anti-cancer therapies in individual patients harboring genetic alterations in their cancer 12 that specifically render it vulnerable. We investigated the potential for high-resolution 13 phenomic analysis in yeast to predict such genetic vulnerabilities by systematic, 14 comprehensive, and quantitative assessment of drug-gene interaction for gemcitabine 15 and cytarabine, substrates of deoxycytidine kinase that have similar molecular structures 16 yet distinct anti-tumor efficacy. Human deoxycytidine kinase (dCK) was conditionally 17 expressed in the S. cerevisiae genomic library of knockout and knockdown (YKO/KD) 18 strains, to globally and quantitatively characterize differential drug-gene interaction for 19 gemcitabine and cytarabine. Pathway enrichment analysis revealed that autophagy, 20 histone modification, chromatin remodeling, and apoptosis-related processes influence 21 gemcitabine specifically, while drug-gene interaction specific to cytarabine was less 22 enriched in Gene Ontology. Processes having influence over both drugs were DNA 23 repair and integrity checkpoints and vesicle transport and fusion. Non-GO-enriched 24 genes were also informative. Yeast phenomic and cancer cell line pharmacogenomics 25 data were integrated to identify yeast-human homologs with correlated differential gene 26 2 expression and drug-efficacy, thus providing a unique resource to predict whether 27 differential gene expression observed in cancer genetic profiles are causal in tumor-28 specific responses to cytotoxic agents. 29 30 Keywords: 31 yeast phenomics, gene-drug interaction, genetic buffering, quantitative high 32 throughput cell array phenotyping (Q-HTCP), cell proliferation parameters (CPPs), 33 gemcitabine, cytarabine, recursive expectation-maximization clustering (REMc), 34 pharmacogenomics 35 36 Introduction: 37Genomics has enabled targeted therapy aimed at cancer driver genes and 38 oncogenic addiction [1], yet traditional cytotoxic chemotherapeutic agents remain among 39 the most widely used and efficacious anti-cancer therapies [2]. Changes in the genetic 40 network underlying cancer can produce vulnerabilities to cytotoxic chemotherapy that 41 further influence the therapeutic window and provide additional insight into their 42 mechanisms of action [3,4]. A potential advantage of so-called synthetic lethality-based 43 treatment strategies is that they could have efficacy against passenger gene mutation or 44 compensatory gene expression, while classic targeted therapies are directed primarily at 45 driver genes ( Fig. 1A). Quantitative high throughput cell array phenotyping of the yeast 46 knockout and knockdown libraries provides a phenomic means for systems level, high- 47resolution modeling of gene interaction [5][6][7][8][9], which is applied here to predict cancer-48 relevant drug-gene interaction through integration with cancer pharmacogenomics 49 resources ( Fig. 1B). 50Nucleoside analogs include a diverse group of co...

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“…The prognostic signi cance of SIRT6 expression might be related to the role of SIRT6 on the proliferation of cancer cells, and SIRT6 is known as an important regulator of cellular proliferation [13][14][15][16]. However, the impact of SIRT6 on the proliferation of cancer cells has been reported controversially [13][14][15][16].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, loss of SIRT6 is a factor associated with shorter survival of breast and liver cancer patients in other reports [13,20]. Even with the same MDA-MB-231 breast cancer cells, there are con icting reports of SIRT6 either increasing or decreasing the proliferation of these cells [13,14]. These controversial reports on the role of SIRT6 in cancer growth suggest that the effect of SIRT6 expression might differ according to the condition of the cancer itself or the cancer-associated environment.…”

Section: Introductionmentioning

confidence: 95%

Inhibition of SIRT6 Potentiates the Anti-Tumor Effect of Doxorubicin through Suppression of the DNA Damage Repair Pathway in Osteosarcoma

Zhang

Moon

et al. 2020

Preprint

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Background SIRT6 has diverse roles in cells, and the role of SIRT6 in tumorigenesis is controversial. Considering the role of SIRT6 as an inducer of DNA damage repair, it might be involved in resistance to anti-cancer therapy. Methods We evaluated the prognostic significance of SIRT6 in 37 osteosarcomas and investigated the therapeutic efficacy of SIRT6 on the anticancer effects of doxorubicin, olaparib, and ATM inhibitor. Results Immunohistochemical expression of SIRT6 was significantly associated with shorter overall survival and relapse-free survival of osteosarcoma patients, especially in patients who received adjuvant chemotherapy. In U2OS and KHOS/NP osteosarcoma cells, knock-down of SIRT6 significantly potentiated apoptotic effects of doxorubicin and SIRT6 overexpression induced resistance to doxorubicin. Moreover, SIRT6 induced the DNA damage repair pathway and SIRT6-mediated resistance to doxorubicin was attenuated by blocking the DNA damage repair pathway with olaparib and ATM inhibitor. Conclusions This study suggests that suppression of SIRT6 in combination with doxorubicin might be an effective modality in the treatment of osteosarcoma patients, especially for osteosarcomas with shorter survival with high expression of SIRT6.

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CK2α/CSNK2A1 Phosphorylates SIRT6 and Is Involved in the Progression of Breast Carcinoma and Predicts Shorter Survival of Diagnosed Patients

Cited by 73 publications

References 52 publications

FAM83H is involved in the progression of hepatocellular carcinoma and is regulated by MYC

FAM83H is involved in the progression of hepatocellular carcinoma and is regulated by MYC

A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity

Inhibition of SIRT6 Potentiates the Anti-Tumor Effect of Doxorubicin through Suppression of the DNA Damage Repair Pathway in Osteosarcoma

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