ZNF32 contributes to the induction of multidrug resistance by regulating TGF-β receptor 2 signaling in lung adenocarcinoma

Li, Jun; Ao, Jie; Li, Kai; Zhang, Jie; Li, Yanyan; Zhang, Le; Wei, Yong; Gong, Di; Gao, Junping; Tan, Weiwei; Huang, Lei; Liu, Lunxu; Lin, Ping; Wei, Yuquan

doi:10.1038/cddis.2016.328

Cited by 17 publications

(21 citation statements)

References 54 publications

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“…Moreover, the mouse homologue of the ZNF32 gene, Zfp637, could markedly increase mTERT expression and telomerase activity and maintain telomere length 25 . As we recently reported, ZNF32 contributes to multidrug resistance in lung adenocarcinoma 26 . Because stem cells are predicted to be responsible for tumour resistance and to influence the effects of therapy, and since more mammospheres are observed in breast cancer cells that over-express ZNF32 during suspension culture, we hypothesized that there may be a relationship between ZNF32 and breast cancer stem cell-like properties.…”

Section: Introductionsupporting

confidence: 57%

“…The intracellular mechanisms regulating breast cancer stem cell-like populations have been gaining attention. The roles of ZNF32 and GPER in mediating proliferation and drug resistance have been recently highlighted 26 , 48 , 49 . However, the role of ZNF32 and GPER in breast cancer stem cell-like properties and their functional significance have remained rather enigmatic.…”

Section: Discussionmentioning

confidence: 99%

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Zinc finger protein 32 promotes breast cancer stem cell-like properties through directly promoting GPER transcription

Gong

Zhang

et al. 2018

Cell Death Dis

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Breast cancer is one of the leading causes of death in women. Due to the existence of a small fraction of stem cell-like subpopulations, some breast cancer subtypes exhibit very high malignancy and resistance to multiple therapies. The underlying mechanisms of how these subtypes acquire stem cell-like properties and progress more aggressively remain largely unknown. Zinc finger protein 32 (ZNF32), a newly discovered transcription factor, has been reported to be associated with breast cancer progression. However, many questions remain about its target genes and its exact mechanisms in regulating stem cell-like properties and drug resistance. In the present study, we examined the relationship between ZNF32 and GPER, a membrane-associated estrogen receptor, and we addressed their roles in stemness regulation in human breast cancer cell lines. Our results showed that ZNF32 could induce expansion of stem cell-like subpopulations and increase drug resistance by upregulating GPER expression, in which ERK activation was also implicated. We also illustrated that ZNF32 induced GPER expression via a ZNF32 binding sequence located within the GPER promoter region. A correlation between ZNF32/GPER expression and increased tumor incidence and burden was observed in xenograft mouse models. We conclude that ZNF32 can engage GPER/ERK signalling and confer breast cancer stem cell-like properties, which may indicate poor prognosis of breast cancer patients. ZNF32 and GPER targeted therapies might provide new solutions for breast cancer treatment.

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Section: Introductionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Zinc finger protein 32 promotes breast cancer stem cell-like properties through directly promoting GPER transcription

Gong

Zhang

et al. 2018

Cell Death Dis

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“…In contrast, another study suggested that high expression of TGFBR2 may be a poor prognostic indicator for overall survival in estrogen receptor α‐negative breast cancer . Li et al also showed that zinc finger protein 32, an important transcription factor associated with cancer, binds to the TGFBR2 promoter and elevates its expression at the mRNA and protein levels, thereby increasing drug resistance in lung cancer. Consistent with this, our results showed that TGFBR2 was highly expressed in rectal cancer cells and tissues.…”

Section: Discussionmentioning

confidence: 99%

Effects of metformin and phenformin on apoptosis and epithelial‐mesenchymal transition in chemoresistant rectal cancer

et al. 2019

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Recurrence and chemoresistance in colorectal cancer remain important issues for patients treated with conventional therapeutics. Metformin and phenformin, previously used in the treatment of diabetes, have been shown to have anticancer effects in various cancers, including breast, lung and prostate cancers. However, their molecular mechanisms are still unclear. In this study, we examined the effects of these drugs in chemoresistant rectal cancer cell lines. We found that SW837 and rectal cancer cells were more resistant to ionizing radiation and 5‐fluorouracil than HCT116 and LS513 colon cancer cells. In addition, metformin and phenformin increased the sensitivity of these cell lines by inhibiting cell proliferation, suppressing clonogenic ability and increasing apoptotic cell death in rectal cancer cells. Signal transducer and activator of transcription 3 and transforming growth factor‐β/Smad signaling pathways were more activated in rectal cancer cells, and inhibition of signal transducer and activator of transcription 3 expression using an inhibitor or siRNA sensitized rectal cancer cells to chemoresistant by inhibition of the expression of antiapoptotic proteins, such as X‐linked inhibitor of apoptosis, survivin and cellular inhibitor of apoptosis protein 1. Moreover, metformin and phenformin inhibited cell migration and invasion by suppression of transforming growth factor β receptor 2‐mediated Snail and Twist expression in rectal cancer cells. Therefore, metformin and phenformin may represent a novel strategy for the treatment of chemoresistant rectal cancer by targeting signal transducer and activator of transcription 3 and transforming growth factor‐β/Smad signaling.

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“…In recent years, several experimental studies revealed a role of ZNF281 (C2H2-type) in tumorigenesis and tumour invasion. ZNF281 is involved in two crucial processes in cancer: the DNA damage response (DDR) 62–65 and the epithelial–mesenchymal transition (EMT). ZNF281 expression is increased upon DNA damage induced by drugs in several cancer types.…”

Section: Role Of Znfs In Diseasesmentioning

confidence: 99%

Zinc-finger proteins in health and disease

et al. 2017

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Zinc-finger proteins (ZNFs) are one of the most abundant groups of proteins and have a wide range of molecular functions. Given the wide variety of zinc-finger domains, ZNFs are able to interact with DNA, RNA, PAR (poly-ADP-ribose) and other proteins. Thus, ZNFs are involved in the regulation of several cellular processes. In fact, ZNFs are implicated in transcriptional regulation, ubiquitin-mediated protein degradation, signal transduction, actin targeting, DNA repair, cell migration, and numerous other processes. The aim of this review is to provide a comprehensive summary of the current state of knowledge of this class of proteins. Firstly, we describe the actual classification of ZNFs, their structure and functions. Secondly, we focus on the biological role of ZNFs in the development of organisms under normal physiological and pathological conditions.

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ZNF32 contributes to the induction of multidrug resistance by regulating TGF-β receptor 2 signaling in lung adenocarcinoma

Cited by 17 publications

References 54 publications

Zinc finger protein 32 promotes breast cancer stem cell-like properties through directly promoting GPER transcription

Zinc finger protein 32 promotes breast cancer stem cell-like properties through directly promoting GPER transcription

Effects of metformin and phenformin on apoptosis and epithelial‐mesenchymal transition in chemoresistant rectal cancer

Zinc-finger proteins in health and disease

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