Biological and clinical significance of NAC1 expression in cervical carcinomas: a comparative study between squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas

Yeasmin, Sabina; Nakayama, Kentaro; Rahman, Mohammed Tanjimur; Rahman, Munmun; Ishikawa, Masatoshi; Katagiri, Atsuko; Iida, Kouji; Nakayama, Naomi; Otuski, Yoshiro; Kobayashi, Hiroshi; Nakayama, Shinichi; Miyazaki, Kohji

doi:10.1016/j.humpath.2011.05.021

Cited by 38 publications

(36 citation statements)

References 26 publications

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“…NAC1 has emerged as a critical molecule that participates in several biological and pathological processes, including addiction to psychostimulants [2,3] and cancer aggressiveness [8–16]. By comparing phenotypes between Nacc1 -/- (knockout) and Nacc1 +/+ (wild type) mice, we sought to elucidate the role(s) of Nacc1 in regulating embryonic development and tissue homeostasis.…”

Section: Discussionmentioning

confidence: 99%

“…NAC1 also was found to maintain the proliferative capacity and stemness of mouse embryonic stem cells [6] by acting in association with homeobox protein Nanog and other nuclear factors [7]. In human cancers, NACC1 upregulation is associated with disease aggressiveness, development of resistance to chemotherapeutic agents, and tumor recurrence in ovarian, endometrial, and cervical carcinomas [8–16]. Moreover, analysis of The Cancer Genome Atlas (TCGA) ovarian cancer data revealed that NACC1 is one of the top genes that shows a significant positive correlation between DNA and RNA copy number [15,17], indicating that NAC1 is a potential “driver” in promoting cancer development through multiple mechanisms related to transcription-dependent and -independent pathways.…”

Section: Introductionmentioning

confidence: 99%

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Loss of NAC1 Expression Is Associated with Defective Bony Patterning in the Murine Vertebral Axis

et al. 2013

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NAC1 encoded by NACC1 is a member of the BTB/POZ family of proteins and participates in several pathobiological processes. However, its function during tissue development has not been elucidated. In this study, we compared homozygous null mutant Nacc1-/- and wild type Nacc1+/+ mice to determine the consequences of diminished NAC1 expression. The most remarkable change in Nacc1-/- mice was a vertebral patterning defect in which most knockout animals exhibited a morphological transformation of the sixth lumbar vertebra (L6) into a sacral identity; thus, the total number of pre-sacral vertebrae was decreased by one (to 25) in Nacc1-/- mice. Heterozygous Nacc1+/- mice had an increased tendency to adopt an intermediate phenotype in which L6 underwent partial sacralization. Nacc1-/- mice also exhibited non-closure of the dorsal aspects of thoracic vertebrae T10-T12. Chondrocytes from Nacc1+/+ mice expressed abundant NAC1 while Nacc1-/- chondrocytes had undetectable levels. Loss of NAC1 in Nacc1-/- mice was associated with significantly reduced chondrocyte migratory potential as well as decreased expression of matrilin-3 and matrilin-4, two cartilage-associated extracellular matrix proteins with roles in the development and homeostasis of cartilage and bone. These data suggest that NAC1 participates in the motility and differentiation of developing chondrocytes and cartilaginous tissues, and its expression is necessary to maintain normal axial patterning of murine skeleton.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Loss of NAC1 Expression Is Associated with Defective Bony Patterning in the Murine Vertebral Axis

et al. 2013

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“…Bimax1 treatment of HeLa cells impaired nuclear localization of NAC1, an oncogenic nuclear protein involved in ovarian cancers and cervical carcinomas [114, 115]. Another cell-permeable SN52 peptide was shown to block nuclear import of NF-κB family members, p52 and RelB, through competing with p52/RelB for nuclear import proteins [116].…”

Section: Targeting Protein Subcellular Localization For Cancer Thementioning

confidence: 99%

Protein mislocalization: Mechanisms, functions and clinical applications in cancer

Wang

2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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The changes from normal cells to cancer cells are primarily regulated by genome instability, which foster hallmark functions of cancer through multiple mechanisms including protein mislocalization. Mislocalization of these proteins, including oncoproteins, tumor suppressors, and other cancer-related proteins, can interfere with normal cellular function and cooperatively drive tumor development and metastasis. This review describes the cancer-related effects of protein subcellular mislocalization, the related mislocalization mechanisms, and the potential application of this knowledge to cancer diagnosis, prognosis, and therapy.

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“…Nucleus accumbens-associated 1 (NAC1) encoded by NACC1 is a member of the family, and the gene was first identified by the observation that the level of NAC1 transcript was elevated in the rat nucleus accumbens in response to cocaine administration (4). Subsequently, NAC1 has been shown to participate in diverse biological functions ranging from maintenance of stemness and proliferation of embryonic stem cells (5, 6) to the pathogenesis of human cancer (7–12). Like other members of the BTB family, the homodimeric or heterodimeric interaction mediated by its BTB domain is thought to be essential for the various functional activities of NAC1 (7).…”

Section: Introductionmentioning

confidence: 99%

NAC1 Is an Actin-Binding Protein That Is Essential for Effective Cytokinesis in Cancer Cells

et al. 2012

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NAC1 is a transcriptional co-repressor protein that is essential to sustain cancer cell proliferation and migration. However, the underlying molecular mechanisms of NAC1 function in cancer cells remain unknown. In this study, we show that NAC1 functions as an actin monomer binding protein. The conserved BTB protein interaction domain in NAC1 is the minimal region for actin binding. Disrupting NAC1 complex function by dominant negative or siRNA strategies reduced cell retraction and abscission during late stage cytokinesis, causing multinucleation in cancer cells. In Nac1-deficient murine fibroblasts, restoring NAC1 expression was sufficient to partially avert multinucleation. We found that siRNA-mediated silencing of the actin binding protein profilin-1 in cancer cells caused a similar multinucleation phenotype and that NAC1 modulated the binding of actin to profillin-1. Taken together, our results indicate that the NAC1/actin/profilin-1 complex is crucial for cancer cell cytokinesis, with a variety of important biological and clinical implications.

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Biological and clinical significance of NAC1 expression in cervical carcinomas: a comparative study between squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas

Cited by 38 publications

References 26 publications

Loss of NAC1 Expression Is Associated with Defective Bony Patterning in the Murine Vertebral Axis

Loss of NAC1 Expression Is Associated with Defective Bony Patterning in the Murine Vertebral Axis

Protein mislocalization: Mechanisms, functions and clinical applications in cancer

NAC1 Is an Actin-Binding Protein That Is Essential for Effective Cytokinesis in Cancer Cells

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