ATPase family AAA domain-containing 3A is a novel anti-apoptotic factor in lung adenocarcinoma cells

Fang, Hsin‐Yuan; Chang, Chia‐Yi; Hsu, Shu‐Han; Huang, Chih‐Yang; Chiang, Shu‐Fen; Chiou, Shiow-Her; Huang, Chaoran; Hsiao, Yu–Cheng; Lin, Tze–Yi; Chiang, I-Ping; Hsu, Wen Hu; Sugano, Sumio; Chen, Chih-Yi; Lin, Ching‐Yuang; Ko, Wen‐Je; Chow, Kuan‐Chih

doi:10.1242/jcs.062034

Cited by 85 publications

(176 citation statements)

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“…Similarly, we find that cells expressing high levels of MYC have an enhanced dependence on ATAD3A for survival, suggesting that targeting ATAD3A may also be effective against MYC-dependent tumor cells. ATAD3A has anti-apoptotic functions in tumors, potentially via its effects on mitochondrial dynamics 33,45 . Collectively, our findings suggest that individual genes encoding rate-limiting proteins involved in basic cell biological processes respond to the difference between physiological and supraphysiological MYC levels and that OmoMYC specifically inhibits tumor cell growth since it suppresses expression of this group of genes.…”

Section: Discussionmentioning

confidence: 99%

OmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors

et al. 2016

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Section: Discussionmentioning

confidence: 99%

OmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors

et al. 2016

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“…Immunohistochemical staining was performed on paraffin-embedded tissues by an immunoperoxidase method as previously described (6,(14)(15)(16)(17)(18). Following removal of paraffin with xylene and alcohol, pathological sections were incubated with antibodies specific to ATAD3A (18), hepatocyte growth factor (HGF), HGF receptor (HGFR, or product of proto-oncogene c-met, c-MET), IL-8 (R&D Systems, Minneapolis, MN) or Ki-67 (zymed, San Francisco, CA). The slides were then treated with peroxidase-conjugated secondary antibodies, and developed in 3-amino-9-ethylcarbazole (AEC).…”

Section: Methodsmentioning

confidence: 99%

“…The non-tumor counterpart of the cervical tissue served as a negative control, and a section of mouse liver tissue was used as positive control for each run of immunohistochemical staining. The same antibodies were used for immunoblotting, which was performed as previously (14)(15)(16)(17)(18).…”

Section: Methodsmentioning

confidence: 99%

“…Nevertheless, since DDH does not directly inactivate anticancer chemotherapeutics, the pro-tumorigenic effects are yet to be clarified. Recently, using suppression subtractive hybridization, oligonucleotide microarray, hierarchical clustering and subsequent gene pool analysis, we identified several interesting genes, such as dynamin-related protein 1 (DRP1) (17), mitofusin 2 (Mfn2) and ATPase family, AAA domain containing 3A (ATAD3A) (18), which were associated with drug resistance of lung cancer cells. DRP1 and Mfn2 are GTPases, and ATAD3A is an ATPase.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, serum deprivation increased protein levels of ATAD3A and cisplatin resistance. Silencing of ATAD3A expression, however, increased cisplatin sensitivity, mitochondrial fragmentation and cellular autophagy, suggesting that ATAD3A could be an anti-apoptotic factor, essential for maintaining the mitochondrial integrity (18). However, the role of ATAD3A expression in UCC has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

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Human papillomavirus infection and expression of ATPase family AAA domain containing 3A, a novel anti-autophagy factor, in uterine cervical cancer

Chen

Hung²,

Lin

et al. 2011

Int J Mol Med

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Abstract. Our aim was to determine the association of human papillomavirus (HPV) infection with the expression of ATPase family AAA domain containing 3A (ATAD3A), an anti-autophagy factor, in uterine cervical cancer (UCC). The HPV genotype was determined by an Easychip HPV blot assay. ATAD3A expression was determined by immunohistochemical staining. High-risk HPV (hrHPV) was detected in 184 (88.9%) of 207 UCC cases. ATAD3A expression was detected in 164 (79.2%) UCC cases. A significant correlation was found between ATAD3A expression and the presence of hrHPV (p<0.001), FIGO stage (p=0.014), lymph node involvement (p=0.001), c-MET expression (p<0.001), interleukin-8 (p=0.03) and patient survival (p=0.0016). Interestingly, silencing of E6/E7 expression decreased ATAD3A expression and cell survival. Moreover, knockdown of ATAD3A (ATAD3A kd ) expression or addition of resveratrol, increased cellular autophagy and apoptosis and reduced drug resistance. Resveratrol reduced ATAD3A expression, and increased abrasion of the mitochondrial outer membrane as well as numbers of autophagosomes, the phenomena that were frequently found in ATAD3A kd cells. In conclusion, our results show that HPV infection correlates with increased ATAD3A expression and drug resistance in UCC. Persistent HPV infection may stabilize ATAD3A expression to inhibit cell autophagy and apoptosis as well as to increase drug resistance. IntroductionUterine cervical cancer (UCC) is the most prevalent cancer, and the fifth leading cause of cancer-related deaths in Taiwanese women (1). High incidence and mortality of the disease was in part due to the conservative attitude toward the Papanicolaou smear, because even though the disease could be detected at the early stages the method was considered intrusive, and in part due to the high infection rate of human papillomavirus (HPV) among the diseased women (2). HPV infection is a potential etiologic cause for UCC development (3,4). Among 95 known HPV (5), genotypes 16, 18, 52 and 58 are categorized as high-risk and most frequently detected in Taiwanese UCC patients (6-9). Carcinogenicity of the high-risk HPV (hrHRV) is closely associated with E6 and E7 proteins, which can respectively inhibit activities of tumor suppressors, p53 and retinoblastoma protein (pRB), to interrupt cell growth regulation (10). Besides carcinogenesis, persistent HPV infection further correlates with tumor recurrence, cancer cell radiosensitivity and the resulting poor prognosis (11-13).Oncogene activation is also crucial for tumorigenesis and cancer progression; in particular, genes that are associated with disease advancement and, possibly, resistance to irradiation and anticancer chemotherapeutics. By using differential display, we have identified overexpression of dihydrodiol dehydrogenase (DDH) in non-small cell lung cancer (14). Using microarrays, we further found that DDH was overexpressed in cisplatin-resistant ovarian cancer cells (15). Clinically, patients with elevated DDH have a higher tumor recurrence rate and lymph node...

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Targeting ATAD3A Phosphorylation Mediated by TBK1 Ameliorates Senescence‐Associated Pathologies

He,

Liu,

Zheng

et al. 2024

Advanced Science

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Targeting cellular senescence, one of the hallmarks of aging and aging‐related pathologies emerges as an effective strategy for anti‐aging and cancer chemotherapy. Here, a switch from TBK1‐OPTN axis to TBK1‐ATAD3A axis to promote cellular senescence is shown. Mechanically, TBK1 protein is abnormally activated and localized to the mitochondria during senescence, which directly phosphorylates ATAD3A at Ser321. Phosphorylated ATAD3A is significantly elevated in cellular senescence as well as in physiological and pathological aging and is essential for suppressing Pink1‐mediated mitophagy by facilitating Pink1 mitochondrial import. Inhibition of ATAD3A phosphorylation at Ser321 by either TBK1 deficiency or by a Ser321A mutation rescues the cellular senescence. A blocking peptide, TAT‐PEP, specifically abrogating ATAD3A phosphorylation, results in elevated cell death by preventing doxorubicin‐induced senescence, thus leading to enhanced tumor sensitivity to chemotherapy. TAT‐PEP treatment also ameliorates various phenotypes associated with physiological aging. Collectively, these results reveal the TBK1‐ATAD3A‐Pink1 axis as a driving force in cellular senescence and suggest a potential mitochondrial target for anti‐aging therapy.

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ATPase family AAA domain-containing 3A is a novel anti-apoptotic factor in lung adenocarcinoma cells

Cited by 85 publications

References 31 publications

OmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors

OmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors

Human papillomavirus infection and expression of ATPase family AAA domain containing 3A, a novel anti-autophagy factor, in uterine cervical cancer

Targeting ATAD3A Phosphorylation Mediated by TBK1 Ameliorates Senescence‐Associated Pathologies

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