Abstract:
:Colon cancer is one of the three common malignant tumors, with a lower survival rate. Ipatasertib, a novel highly selective ATP-competitive pan-Akt inhibitor, shows a strong antitumor effect in a variety of carcinoma, including colon cancer. However, there is a lack of knowledge about the precise underlying mechanism of clinical therapy for colon cancer. We conducted this study to determine that ipatasertib prevented colon cancer growth through PUMA-dependent apoptosis. Ipatasertib led to p53-independent PUMA activation by inhibiting Akt, thereby activating both FoxO3a and NF-κB synchronously that will directly bind to PUMA promoter, up-regulating PUMA transcription and Bax-mediated intrinsic mitochondrial apoptosis. Remarkably, Akt/FoxO3a/PUMA is the major pathway while Akt/NF-κB/PUMA is the secondary pathway of PUMA activation induced by ipatasertib in colon cancer. Knocking out PUMA eliminated ipatasertib-induced apoptosis both in vitro and in vivo (xenografts). Furthermore, PUMA is also indispensable in combinational therapies of ipatasertib with some conventional or novel drugs. Collectively, our study demonstrated that PUMA induction by FoxO3a and NF-κB is a critical step to suppress the growth of colon cancer under the therapy with ipatasertib, which provides some theoretical basis for clinical assessment.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Sun L,Huang Y,Liu Y,Zhao Y,He X,Zhang L,Wang F,Zhang Ydoi
10.1038/s41419-018-0943-9subject
Has Abstractpub_date
2018-09-05 00:00:00pages
911issue
9issn
2041-4889pii
10.1038/s41419-018-0943-9journal_volume
9pub_type
杂志文章abstract::In the healthcare sector, phytocompounds are known to be beneficial by contributing or alleviating a variety of diseases. Studies have demonstrated the progressive effects of phytocompounds on immune-related diseases and to exhibit anticancer effects. Graviola tree is an evergreen tree with its extracts (leafs and see...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0772-x
更新日期:2018-07-09 00:00:00
abstract::Extracorporeal photochemotherapy (ECP) is employed for the management of cutaneous T cell lymphoma (CTCL). ECP involves the extracorporeal exposure of white blood cells (WBCs) to a photosensitizer, 8-methoxypsoralen (8-MOP), in the context of ultraviolet A (UVA) radiation, followed by WBC reinfusion. Historically, the...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1819-3
更新日期:2019-08-02 00:00:00
abstract::Mammalian female fertility is limited by the number and quality of oocytes in the ovarian reserve. The number of oocytes is finite since all germ cells cease proliferation to become oocytes in fetal life. Moreover, 70-80% of the initial oocyte population is eliminated during fetal and neonatal development, restricting...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2019-x
更新日期:2019-10-17 00:00:00
abstract::Detailed understanding of the mechanistic steps underlying tumor initiation and malignant progression is critical for insights of potentially novel therapeutic modalities. Cellular reprogramming is an approach of particular interest because it can provide a means to reset the differentiation state of the cancer cells ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.189
更新日期:2016-07-28 00:00:00
abstract::Caveolin-1 (CAV1) is a crucial regulator of lipid accumulation and metabolism. Previous studies have shown that global Cav1 deficiency affects lipid metabolism and hepatic steatosis. We aimed to analyze the consequences of hepatocyte-specific Cav1 knockout under healthy conditions and upon non-alcoholic fatty liver di...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2295-5
更新日期:2020-02-06 00:00:00
abstract::Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.211
更新日期:2015-08-13 00:00:00
abstract::Polo-like kinase 1 (PLK1) is an important mitotic kinase and its expression is tightly regulated in the cell cycle and in the DNA damage response. PLK1 expression is previously shown to be suppressed by p53 and/or p21. Here, we demonstrate that the CCAAT box in the PLK1 promoter is pivotal for p53/p21-mediated PLK1 re...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.527
更新日期:2014-01-09 00:00:00
abstract::Autophagy (macroautophagy) is an evolutionarily conserved lysosomal degradation process, in which a cell degrades long-lived proteins and damaged organelles. Recently, accumulating evidence has revealed the core molecular machinery of autophagy in carcinogenesis; however, the intricate relationship between autophagy a...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2013.422
更新日期:2013-10-31 00:00:00
abstract::Quantitative and kinetic analyses of apoptotic cell death are integral components of exploring cell biology, measuring cellular stress responses, and performing high-throughput genomic/RNAi/drug screens. Here, we present a detailed method that integrates robust kinetic real-time high-content imaging with Annexin V lab...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.332
更新日期:2016-12-01 00:00:00
abstract::The emergence of drug resistant tumours that are able to escape cell death pose a major problem in the treatment of cancers. Tumours develop resistance to DNA-damaging chemotherapeutic agents by acquiring the ability to repair their DNA. Combination therapies that induce DNA damage and disrupt the DNA damage repair pr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.365
更新日期:2013-10-10 00:00:00
abstract::BMP2 expression is spatiotemporally correlated with embryo implantation and is crucial for endometrial decidualization and fertility in mice. BMP2 has been reported to increase the mesenchymal adhesion molecule N-cadherin and enhance cell invasion in cancer cells; moreover, studies suggest that N-cadherin promotes pla...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0230-1
更新日期:2018-02-07 00:00:00
abstract::Abdominal Aortic aneurysm (AAA) is associated with chronic inflammation, cells apoptosis, and impairment of autophagy. BP-1-102, a novel potent STAT3 inhibitor, has been recently reported to significantly block inflammation-related signaling pathways of JAK2/STAT3 and NF-κB, as well as regulate autophagy. However, its...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2326-2
更新日期:2020-02-18 00:00:00
abstract::DEP-domain containing mTOR-interacting protein (DEPTOR), a natural mTOR inhibitor, has essential roles in several processes, including cell growth, metabolism, apoptosis, and immunity. DEPTOR expression has been shown to be diversely controlled at transcriptional levels in cell- and context-specific manners. However, ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03185-3
更新日期:2020-11-12 00:00:00
abstract::G-protein-coupled receptor (GPCR)-related proteins are dysregulated and the GPCR CC-chemokine receptor 10 (CCR10) is significantly upregulated in inflammation-driven HCC. However, CCR10's role in inflammation-driven hepatocarcinogenesis remains unknown. The aim of this study was to evaluate the role of CCR10 in inflam...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0267-9
更新日期:2018-02-14 00:00:00
abstract::Epigenetic alteration of tumor suppression gene is one of the most significant indicators in human esophageal squamous cell carcinoma (ESCC). In this study, we identified a novel ESCC hypermethylation biomarker ZNF132 by integrative computational analysis to comprehensive genome-wide DNA methylation microarray dataset...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1236-z
更新日期:2018-12-18 00:00:00
abstract::Cancer stem cells (CSCs) represent a population of cancer cells that possess unique self-renewal and differentiation characteristics required for tumorigenesis and are resistant to chemotherapy-induced apoptosis. Lung CSCs can be enriched by several markers including drug-resistant side population (SP), CD133(pos) and...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.93
更新日期:2012-07-19 00:00:00
abstract::The control of glucose metabolism and the cell cycle must be coordinated in order to guarantee sufficient ATP and anabolic substrates at distinct phases of the cell cycle. The family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) are well established regulators of glucose metabolism via their synt...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.292
更新日期:2014-07-17 00:00:00
abstract::Novel therapeutic targets are required to protect the heart against cell death from acute ischemia-reperfusion injury (IRI). Mutations in the DJ-1 (PARK7) gene in dopaminergic neurons induce mitochondrial dysfunction and a genetic form of Parkinson's disease. Genetic ablation of DJ-1 renders the brain more susceptible...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.41
更新日期:2014-02-27 00:00:00
abstract::A proper number of oligodendrocytes in the nerve system is essential for neuronal functions. In the olfactory bulb (OB), enriched oligodendrocytes are crucial for olfactory information processing. However, how the precise number of oligodendrocytes in the OB is regulated remains elusive. Here we identified that the tr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03371-3
更新日期:2021-01-18 00:00:00
abstract::Increasing the sensitivity of glioblastoma cells to radiation is a promising approach to improve survival in patients with glioblastoma multiforme (GBM). This study aims to determine if serine/threonine phosphatase (protein phosphatase 6 (PP6)) is a molecular target for GBM radiosensitization treatment. The GBM orthot...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.126
更新日期:2011-12-08 00:00:00
abstract::Kidney aging leads to an increased incidence of end-stage renal disease (ESRD) in the elderly, and aging is a complex biological process controlled by signaling pathways and transcription factors. Podocyte senescence plays a central role in injury resulting from kidney aging. Here, we demonstrated the critical role of...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1933-2
更新日期:2019-09-17 00:00:00
abstract::Obesity-related kidney diseases are becoming serious health problems worldwide, yet the mechanism by which obesity causes kidney injury is not fully understood. The purpose of current study was to investigate the role of Mas receptor in lipid-induced kidney injury. In mice fed with high-fat diet (HFD), the protein abu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03375-z
更新日期:2021-01-21 00:00:00
abstract::Aneuploidy including trisomy results in developmental disabilities and is the leading cause of miscarriages in humans. Unlike trisomy 21, pathogenic mechanisms of trisomy 18 remain unclear. Here, we successfully generated induced pluripotent stem cells (iPSCs) from human amniotic fluid cells (AFCs) with trisomy 18 pre...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.565
更新日期:2017-10-26 00:00:00
abstract::Epithelial homeostasis plays an essential role in maintaining endometrial function. But the epithelial role in endometrial fibrosis has been less studied. Previously, we showed that ectopic expression of ΔNp63α is associated with fibrosis process and epithelial dysfunction in endometria of patients with intrauterine a...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2666-y
更新日期:2020-06-11 00:00:00
abstract::Mammalian folliculogenesis is a complex process in which primordial follicles develop into pre-ovulatory follicles, followed by ovulation to release mature oocytes. In this study, we explored the role of miR-144 in ovulation. miR-144 was one of the differentially expressed microRNAs, which showed 5.59-fold changes, in...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.24
更新日期:2017-02-09 00:00:00
abstract::Macrophages are involved in tumor growth and progression. They infiltrate into tumors and cause inflammation, which creates a microenvironment favoring tumor growth and metastasis. However, certain stimuli may induce macrophages to act as tumor terminators. Here we report that the calcineurin B subunit (CnB) synergize...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.92
更新日期:2015-05-07 00:00:00
abstract::Normal cells require adhesion to extracellular matrix for survival. Cell detachment causes a drastic increase in reactive oxygen species (ROS) that promotes anoikis. In the present study, we observed that upon detachment from matrix, human mammary epithelial cells strongly upregulate manganese superoxide dismutase (Mn...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.20
更新日期:2013-02-21 00:00:00
abstract::Triple-negative breast cancers (TNBCs) are aggressive forms of breast carcinoma associated with a high rate of recidivism. In this paper, we report the production of mammospheres from three lines of TNBC cells and demonstrate that both parthenolide (PN) and its soluble analog dimethylaminoparthenolide (DMAPT) suppress...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.94
更新日期:2016-04-14 00:00:00
abstract::We investigated the mechanism underlying the effect of a combination treatment of 125I radioactive seed implantation and lobaplatin (LBP) in hepatocellular carcinoma. The effects of administration of HCC cells and subcutaneous tumor model of mice with different doses of 125I or a sensitizing concentration of LBP alone...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1918-1
更新日期:2019-10-03 00:00:00
abstract::Hepatocellular carcinoma is the sixth most common cancer and gives rise to numerous deaths around the world every year. However, the molecular mechanism that controls hepatocarcinogenesis remains largely unknown. Here we found out an uncharacterized long noncoding RNA named lncAKHE. We found that lncAKHE was highly ex...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0554-5
更新日期:2018-05-01 00:00:00