ZKSCAN3 promotes breast cancer cell proliferation, migration and invasion

Chi, Yan-Yan; Han, Xu; Wang, Feng; Chen, Xiaoling; Shan, Zhengzheng; Sun, Yan; Fan, Qingxia

doi:10.1016/j.bbrc.2018.07.019

Cited by 23 publications

(26 citation statements)

References 23 publications

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“…Finally, as ZKSCAN3 dysregulation contributes to numerous human cancers (Chi et al, 2018; Kawahara et al, 2016; Kim et al, 2016; Lee et al, 2018; Li et al, 2019; Yang et al, 2008; Yang et al, 2011) and that metabolic reprogramming is a hallmark of the tumour microenvironment (reviewed in (Reina-Campos et al, 2017)), the knowledge that Drosophila M1BP and vertebrate ZKSCAN3 are functionally homologous proteins controlling autophagy and metabolic gene expression will allow use of the powerful Drosophila model system to study ZKSCAN3 function in metabolism, autophagy control and cancerogenesis.…”

Section: Resultsmentioning

confidence: 99%

Human ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy regulation

Barthez

Poplineau

Elrefaey

et al. 2019

Preprint

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Autophagy is an essential cellular process that maintains homeostasis by recycling damaged organelles and nutrients during development and cellular stress. ZKSCAN3 is the sole identified master transcriptional repressor of autophagy in humans. How ZKSCAN3 achieves autophagy repression at the mechanistic or organismal level however still remains to be elucidated. Here, we demonstrate that vertebrate ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy repression. Expression of ZKSCAN3 in Drosophila prevents premature autophagy onset due to loss of M1BP function and conversely, M1BP expression in human cells can prevent starvation-induced autophagy due to loss of nuclear ZKSCAN3 function. In Drosophila ZKSCAN3 binds genome-wide to sequences targeted by M1BP and transcriptionally regulates the majority of M1BP-controlled genes. These data allow the potential for transitioning the mechanisms, gene targets and plethora metabolic processes controlled by M1BP onto ZKSCAN3 and opens up Drosophila as a tool in studying the function of ZKSCAN3 in autophagy and tumourigenesis.

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Section: Resultsmentioning

confidence: 99%

Human ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy regulation

Barthez

Poplineau

Elrefaey

et al. 2019

Preprint

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show abstract

“…Finally, as ZKSCAN3 dysregulation contributes to numerous human cancers 43,[46][47][48][49][50][51] and that metabolic reprogramming is a hallmark of the tumour microenvironment (reviewed in 52 ), the knowledge that Drosophila M1BP and vertebrate ZKSCAN3 are functionally homologous proteins controlling autophagy and metabolic gene expression will allow use of the powerful Drosophila model system to study ZKSCAN3 function in metabolism, autophagy control and cancerogenesis.…”

Section: Discussionmentioning

confidence: 99%

Human ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy regulation

Barthez

Poplineau

Elrefaey

et al. 2020

Sci Rep

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Autophagy is an essential cellular process that maintains homeostasis by recycling damaged organelles and nutrients during development and cellular stress. ZKSCAN3 is the sole identified master transcriptional repressor of autophagy in human cell lines. How ZKSCAN3 achieves autophagy repression at the mechanistic or organismal level however still remains to be elucidated. Furthermore, Zkscan3 knockout mice display no discernable autophagy-related phenotypes, suggesting that there may be substantial differences in the regulation of autophagy between normal tissues and tumor cell lines. Here, we demonstrate that vertebrate ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy repression. Expression of ZKSCAN3 in Drosophila prevents premature autophagy onset due to loss of M1BP function and conversely, M1BP expression in human cells can prevent starvation-induced autophagy due to loss of nuclear ZKSCAN3 function. In Drosophila ZKSCAN3 binds genome-wide to sequences targeted by M1BP and transcriptionally regulates the majority of M1BP-controlled genes, demonstrating the evolutionary conservation of the transcriptional repression of autophagy. This study thus allows the potential for transitioning the mechanisms, gene targets and plethora metabolic processes controlled by M1BP onto ZKSCAN3 and opens up Drosophila as a tool in studying the function of ZKSCAN3 in autophagy and tumourigenesis.

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“…ZKSCAN3 is a member of the zinc-finger protein family 1 and is highly expressed in various types of tumor cells, including colon cancer, multiple myeloma, bladder cancer, prostate cancer, breast cancer, and cervical cancer. 2,4,5 In multiple myeloma, for instance, the proliferation of myeloma cells can be inhibited by inhibiting ZKSCAN3 expression using small hairpin RNA. 7 We observed an increase in the number of plasma cells in zks-can3-KO mice.…”

Section: Discussionmentioning

confidence: 99%

“…It promotes the progression, invasion, migration, and growth of tumor cells by upregulating the expression of genes associated with the cell cycle, cell proliferation, migration, angiogenesis, and proteolysis. [2][3][4][5][6][7] In contrast, silencing of its expression significantly suppresses the tumorigenesis, as well as inhibits the xenograft tumorigenicity, growth, and metastasis of tumor cells. Knocking out key molecules in tumor cells may inhibit the growth of tumors or enhance the efficacy of anti-tumor drugs, and thus has gained attention for the treatment of tumors.…”

Section: Introductionmentioning

confidence: 99%

Zkscan3 gene is a potential negative regulator of plasma cell differentiation

Wen

et al. 2019

Eur J Inflamm

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We previously showed that the ZKSCAN3 gene codes for a zinc-finger transcription factor that regulates the expression of important genes and plays crucial roles in the development, metastasis, and pathogenesis of rectal cancer, prostate cancer, myeloma, and so on, and in the regulation of autophagy. However, its biological functions under normal physiological conditions remain unclear. In addition, our previous studies showed that the ZKSCAN3 gene may negatively regulate B cell functions. Therefore, we constructed a zkscan3-knockout mouse model and observed that knockout mice contained a greater number of plasma cells than wild-type mice. We also found that the number of plasma cells was significantly increased in either colorectal cancer xenografts or under lipopolysaccharide-induced conditions. RNAseq and quantitative-polymerase chain reaction assay indicated that the X-inactive-specific transcript is upregulated in B cells of zkscan3-knockout mice, which may represent a potential mechanism how zkscan3 modulates plasma cell differentiation.

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ZKSCAN3 promotes breast cancer cell proliferation, migration and invasion

Cited by 23 publications

References 23 publications

Human ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy regulation

Human ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy regulation

Human ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy regulation

Zkscan3 gene is a potential negative regulator of plasma cell differentiation

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