Tumor-Promoting ATAD2 and Its Preclinical Challenges

Liu, Haicheng; Wen, Qianghai; Yan, Sheng; Zeng, Weikun; Zou, Yuhua; Liu, Quanliang; Zhang, Guoxi; Zou, Junrong; Zou, Xiaofeng

doi:10.3390/biom12081040

Cited by 11 publications

(4 citation statements)

References 143 publications

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“…In breast cancer, ATAD2 has been identified as an ERα coregulatory factor that plays a critical role in ER-mediated activation. ATAD2 is directly associated with estrogen-bound ERα and ACTR, and thus elevates the expression of ERα-targeted cell cycle regulators, such as cyclin D1, Myc, and E2F1, which promote cancer cell proliferation [ 26 , 27 ]. Additionally, ATAD2 could positively mediate the expression of pro-survival genes, including SGK, VEGF, IRS2, and AKT, which contribute to promoting breast cancer progression [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

miR-302 Suppresses the Proliferation, Migration, and Invasion of Breast Cancer Cells by Downregulating ATAD2

Hwang

Park

et al. 2022

Cancers

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Breast cancer is the most common malignant tumor in women. The ATPase family AAA domain-containing protein 2 (ATAD2) contains an ATPase domain and a bromodomain, and is abnormally expressed in various human cancers, including breast cancer. However, the molecular mechanisms underlying the regulation of ATAD2 expression in breast cancer remain unclear. This study aimed to investigate the expression and function of ATAD2 in breast cancer. We found that ATAD2 was highly expressed in human breast cancer tissues and cell lines. ATAD2 depletion via RNA interference inhibited the proliferation, migration, and invasive ability of the SKBR3 and T47D breast cancer cell lines. Furthermore, Western blot analysis and luciferase assay results revealed that ATAD2 is a putative target of miR-302. Transfection with miR-302 mimics markedly reduced cell migration and invasion. These inhibitory effects of miR-302 were restored by ATAD2 overexpression. Moreover, miR-302 overexpression in SKBR3 and T47D cells suppressed tumor growth in the xenograft mouse model. However, ATAD2 overexpression rescued the decreased tumor growth seen after miR-302 overexpression. Our findings indicate that miR-302 plays a prominent role in inhibiting the cancer cell behavior associated with tumor progression by targeting ATAD2, and could thus be a valuable target for breast cancer therapy.

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Section: Discussionmentioning

confidence: 99%

miR-302 Suppresses the Proliferation, Migration, and Invasion of Breast Cancer Cells by Downregulating ATAD2

Hwang

Park

et al. 2022

Cancers

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“…There are two isoforms of human ATAD2, ATAD2A and ATAD2B ( 75 ). However, the majority of published functional studies have been performed on ATAD2A ( 21 , 75 , 76 ). ATAD2 is an emerging oncoprotein, a potential biomarker and a potent cancer drug target.…”

Section: The Bet Family: Brd4 Brd2 and Brd Testis Associated (Brdt)mentioning

confidence: 99%

Essential role of bromodomain proteins in renal cell carcinoma (Review)

et al. 2023

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Histone alterations are a hallmark of kidney cancer. Histone acetylation modification mediated by bromodomain proteins (BRD) has been indicated to be related to a variety of cancer types and several targeted inhibitors have been proven to be promising modalities for cancer adjuvant therapy. As renal cell carcinoma (RCC) is not sensitive to radiotherapy or chemotherapy, the exploration of effective adjuvant therapies remains an important research direction for advanced RCC. At present, studies on bromodomain family proteins in RCC are limited and the roles of bromodomain family proteins in RCC have remained to be fully elucidated. The present review discussed the role of bromodomain family proteins in RCC, aiming to explore possible potential therapeutic targets of BRD-related drugs in this type of cancer.

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“…Liu et al [46] have reviewed several studies that have reported that the ATAD2 can regulate different downstream molecules and is overexpressed in various cancer types, including BC, gastric cancer, pancreatic cancer, colorectal cancer, ovarian cancer, uterine corpus endometrial carcinoma, cervical cancer, prostate cancer, renal cancer, and lung cancer. Due to the fact that ATAD2 is a co-activator of the ERs and the androgen receptors in BC, it mediates the expression of E2 that induces cell proliferation and cell cycle progression in estrogen-dependent tumors [47].…”

Section: Plos Onementioning

confidence: 99%

Proteomic profiling of urinary extracellular vesicles differentiates breast cancer patients from healthy women

Jeanmard,

Bissanum,

Sriplung

et al. 2023

PLoS ONE

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Urinary extracellular vesicles (uEVs) reflect the biological conditions of the producing cells. The protein profiling of uEVs allow us to better understand cancer progression in several cancers such as bladder cancer, prostate cancer and kidney cancer but has not been reported in breast cancer. We have, herein, aimed at quantifying the concentration and at generating the proteomic profile of uEVs in patients with breast cancer (BC) as compared to that of healthy controls (CT). Urine samples were collected from 29 CT and 47 patients with BC. uEVs were isolated by using differential ultracentrifugation, and were then characterized by Western blotting and transmission electron microscopy. Moreover, a nanoparticle tracking analysis was used in order to measure the concentration and the size distribution of urine particles and uEVs. The proteomic profiling of the uEVs was facilitated through LC-MS/MS. The uEV concentration was not significantly different between the assessed groups. The undertaken proteomic analysis revealed 15,473 and 11,278 proteins in the BC patients’ group and the CT group, respectively. Furthermore, a heat map analysis revealed a differential protein expression, while a principal component analysis highlighted two clusters. The volcano plot indicated 259 differentially expressed proteins (DEPs; 155 up- and 104 down-regulated proteins) in patients with BC compared with CT. The up-regulated proteins from BC-derived uEVs were enriched in pathways related to cancer progression (i.e., cell proliferation, cell survival, cell cycle, cell migration, carbohydrate metabolism, and angiogenesis). Moreover, we verified the expression of the upregulated DEPs using UALCAN for web-based validation. Remarkably, the results indicated that 6 of 155 up-regulated proteins (POSTN, ATAD2, BCAS4, GSK3β, HK1, and Ki-67) were overexpressed in BC compared with normal samples. Since these six proteins often act as markers of cell proliferation and progression, they may be potential biomarkers for BC screening and diagnosis. However, this requires validation in larger cohorts.

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Tumor-Promoting ATAD2 and Its Preclinical Challenges

Cited by 11 publications

References 143 publications

miR-302 Suppresses the Proliferation, Migration, and Invasion of Breast Cancer Cells by Downregulating ATAD2

miR-302 Suppresses the Proliferation, Migration, and Invasion of Breast Cancer Cells by Downregulating ATAD2

Essential role of bromodomain proteins in renal cell carcinoma (Review)

Proteomic profiling of urinary extracellular vesicles differentiates breast cancer patients from healthy women

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