Abstract:
:Chemoresistance is one of the leading causes that contributes to tumor relapse and poor patient outcome after several rounds of drug therapy. The causes of chemoresistance are multi-factorial. Ultimately, it is the balance of pro- and anti-apoptotic activities in the cells. We have previously reported links between POPX2 serine/threonine phosphatase with cell motility and invasiveness of breast cancer cells. Here, we show that POPX2 plays a role in the regulation of apoptosis. The effect of POPX2 on apoptosis centers on the inactivation of TGF-β activated kinase (TAK1). TAK1 is essential for several important biological functions including innate immunity, development and cell survival. We find that POPX2 interacts directly with TAK1 and is able to dephosphorylate TAK1. Cells with lower levels of POPX2 exhibit higher TAK1 activity in response to etoposide (VP-16) treatment. This subsequently leads to increased translocation of NF-κB from the cytosol to the nucleus. Consequently, NF-κB-mediated transcription of anti-apoptotic proteins is upregulated to promote cell survival. On the other hand, cells with higher levels of POPX2 are more vulnerable to apoptosis induced by etoposide. Our data demonstrate that POPX2 is a negative regulator of TAK1 signaling pathway and modulates apoptosis through the regulation of TAK1 activity. As inhibition of TAK1 has been proposed to reduce chemoresistance and increase sensitivity to chemotherapy in certain types of cancer, modulation of POPX2 levels may provide an additional avenue and consideration in fine-tuning therapeutic response.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Weng T,Koh CGdoi
10.1038/cddis.2017.443subject
Has Abstractpub_date
2017-09-14 00:00:00pages
e3051issue
9issn
2041-4889pii
cddis2017443journal_volume
8pub_type
杂志文章abstract::N-myc and STAT interactor (NMI) has been proved to bind to different transcription factors to regulate a variety of signaling mechanisms including DNA damage, cell cycle and epithelial-mesenchymal transition. However, the role of NMI in the regulation of cancer stem cells (CSCs) remains poorly understood. In this stud...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.200
更新日期:2017-05-11 00:00:00
abstract::Although Yes-associated protein (YAP) is very important to liver cancer, its nuclear localisation prevents consideration as a promising therapeutic target and a diagnostic biomarker. Recently, we reported that the protumourigenic roles of YAP in liver cancer are indispensable for transcription factor CP2 (TFCP2) in a ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1894-5
更新日期:2019-09-09 00:00:00
abstract::Intestinal epithelial cells (IECs) not only have a critical function in the absorption of nutrients, but also act as a physical barrier between our body and the outside world. Damage and death of the epithelial cells lead to the breakdown of this barrier function and inflammation due to access of the immune system to ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.183
更新日期:2014-05-15 00:00:00
abstract::Transient receptor potential vanilloid type 4 (TRPV4) is a Ca2+-permeable cation channel that is known to be an osmosensor and thermosensor. Currently, limited evidence shows that TRPV4 plays opposite roles in either promoting or inhibiting cancer development in different cancer types. Furthermore, the precise biologi...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1700-4
更新日期:2019-06-12 00:00:00
abstract::The original version of this article contained an error in the name of one of the co-authors (Kayvan Mohkam). This has been corrected in the PDF and HTML versions. ...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-020-2262-1
更新日期:2020-01-23 00:00:00
abstract::The ubiquitination-proteasome and degradation system is an essential process that regulates protein homeostasis. This system is involved in the regulation of cell proliferation, differentiation and survival, and dysregulations in this system lead to pathologies including cancers. The ubiquitination system is an enzyma...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2012.217
更新日期:2013-01-17 00:00:00
abstract::The proapoptotic protein, prostate apoptosis response-4 (Par-4), acts as a tumor suppressor in prostate cancer cells. The serine/threonine kinase casein kinase 2 (CK2) has a well-reported role in prostate cancer resistance to apoptotic agents or anticancer drugs. However, the mechanistic understanding on how CK2 suppo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.532
更新日期:2014-01-23 00:00:00
abstract::Inflammation plays an important role in hypertensive cardiac injury. The endoplasmic reticulum (ER) stress pathway is involved in the inflammatory response. However, the role of ER stress in elevated angiotensin II (Ang II)-induced cardiac injury remains unclear. In this study, we investigated the role of ER stress in...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.164
更新日期:2016-06-09 00:00:00
abstract::Activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) has been implicated in diverse kidney diseases, yet its in vivo significance in diabetic nephropathy (DN) is largely unknown. In the present study, we demonstrated a podocyte-specific Rac1-deficient mouse strain and showed that specific inhibition of Rac1...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0353-z
更新日期:2018-03-01 00:00:00
abstract::Estrogen-dependent breast cancer is often treated with the aromatase inhibitors or estrogen receptor (ER) antagonists. Tamoxifen as a major ER antagonist is usually used to treat those patients with ERα-positive breast cancer. However, a majority of patients with ERα positive fail to respond to tamoxifen due to the pr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.361
更新日期:2016-11-03 00:00:00
abstract::Granzyme B (GZMB) is a proapoptotic serine protease that is released by cytotoxic lymphocytes. However, GZMB can also be produced by other cell types and is capable of cleaving extracellular matrix (ECM) proteins. GZMB contributes to abdominal aortic aneurysm (AAA) through an extracellular, perforin-independent mechan...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.88
更新日期:2011-09-08 00:00:00
abstract::Gallbladder cancer (GBC) is a highly malignant bile duct cancer with poor prognosis due to early invasion and metastasis. However, the molecular mechanisms through which GBC cells interact with the tumor microenvironment (TME) remain poorly understood. Here, we examined the role of the tumor suppressor apoptosis-stimu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1145-1
更新日期:2018-11-02 00:00:00
abstract::Prostate cancer stem cells (PCSCs) play a critical role in prostate cancer progression and metastasis, which remains an obstacle for successful prostate cancer treatment. Tumor-associated macrophages (TAMs) are the most abundant immune cell population within the tumor microenvironment (TME). Systematic investigation o...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2435-y
更新日期:2020-04-16 00:00:00
abstract::Previous studies have shown that miR-203 is a skin-specific microRNA (miRNA) with a profound role in skin cell differentiation. However, emerging microarray and deep sequencing data revealed that miR-203 is also expressed in embryonic skeletal muscle and myoblasts. In this study, we found that miR-203 was transiently ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.289
更新日期:2014-07-17 00:00:00
abstract::Radiotherapy for head and neck cancer is associated with impairment of salivary gland function and consequent xerostomia, which has a devastating effect on the quality of life of the patients. The mechanism of radiation-induced salivary gland damage is not completely understood. Cellular senescence is a permanent stat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03074-9
更新日期:2020-10-14 00:00:00
abstract::Proton pump inhibitors (PPI) target tumour acidic pH and have an antineoplastic effect in melanoma. The PPI esomeprazole (ESOM) kills melanoma cells through a caspase-dependent pathway involving cytosolic acidification and alkalinization of tumour pH. In this paper, we further investigated the mechanisms of ESOM-induc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2010.67
更新日期:2010-10-21 00:00:00
abstract::Autophagy is a major self-degradative process that maintains cellular homeostasis and function in mammalian cells. Autophagic dysfunction occurs in the early pathogenesis of Alzheimer's disease (AD) and directly regulates amyloid-β (Aβ) metabolism. Although it has been proven that the cytokine IFN-γ enhances autophagy...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2644-4
更新日期:2020-06-08 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::The nuclear localization signal (NLS) in kinesin-14 KIFC1 is associated with nuclear importins and Ran gradient, but detailed mechanism remains unknown. In this study, we found that KIFC1 proteins have specific transport characteristics during cell cycle. In the absence of KIFC1, cell cycle kinetics decrease significa...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1619-9
更新日期:2019-05-24 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::Inhibition of human mitochondrial peptide deformylase (HsPDF) depolarizes the mitochondrial membrane, reduces mitochondrial protein translation and causes apoptosis in Burkitt's lymphoma. We showed that HsPDF mRNA and protein levels were overexpressed in cancer cells and primary acute myeloid leukemia samples. Myc reg...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.112
更新日期:2014-03-27 00:00:00
abstract::The majority of developmentally programmed cell death (PCD) is mediated by caspase-dependent apoptosis; however, additional modalities, including autophagy-dependent cell death, have important spatiotemporally restricted functions. Autophagy involves the engulfment of cytoplasmic components in a double membrane vesicl...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1368-9
更新日期:2019-02-08 00:00:00
abstract::Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by dopaminergic neuronal loss that initiates in the substantia nigra pars compacta and by the formation of intracellular inclusions mainly constituted by aberrant α-synuclein (α-syn) deposits known as Lewy bodies. Most cases ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2092-1
更新日期:2019-11-12 00:00:00
abstract::Numerous evidences have shown that circular RNAs (circRNAs) play a key role in regulating the pathogenesis of cancer. However, the mechanism of circRNAs in urothelial carcinoma of bladder (UCB) remains largely unclear. In this study, we found circFAM114A2 was significantly downregulated both in UCB tissue specimens an...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2226-5
更新日期:2020-01-22 00:00:00
abstract::Cancer-initiating cell (CIC) is critical in cancer development, maintenance and recurrence. The reverse expression pattern of coxsackie and adenovirus receptor (CAR) and αν integrin in bladder cancer decreases the infection efficiency of adenovirus. We constructed Arg-Gly-Asp (RGD)-modified oncolytic adenovirus, carry...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.128
更新日期:2015-05-14 00:00:00
abstract::Glial cell line-derived neurotrophic factor (GDNF) has strong neuroprotective and neurorestorative effects on dopaminergic (DA) neurons in the substantia nigra (SN); however, the underlying molecular mechanisms remain to be fully elucidated. In this study, we found that the expression level of transcription factor Six...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.120
更新日期:2016-05-05 00:00:00
abstract::Phosphatase and tensin homolog (PTEN) regulates apoptosis and axonal growth in the developing and adult central nervous system (CNS). Here, we show that human PTEN C-terminal PDZ interactions play a critical role in neuronal apoptosis and axon regeneration after traumatic CNS injury and stroke, highlighted by the find...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1802-z
更新日期:2019-07-29 00:00:00
abstract::Cancer-associated fibroblasts (CAFs) support tumorigenesis by stimulating cancer cell proliferation, and invasion, but how the premalignant stromal fibroblasts trigger epithelial changes remain unclear. We demonstrate that atypical ductal hyperplasia-associated fibroblasts (AHFs) are one kind of activated fibroblasts ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0133-1
更新日期:2018-01-26 00:00:00
abstract::Mitochondrial apoptosis-inducing factor (AIF) influences the oxidative phosphorylation (OXPHOS) system and can be recruited as a mediator of cell death. Pathogenic mutations in the AIFM1 gene cause severe human diseases. Clinical manifestations include inherited peripheral neuropathies, prenatal cerebral abnormalities...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.170
更新日期:2015-07-09 00:00:00
abstract::Hepatocytes undergo the metaplasia into ductal biliary epithelial cells (BECs) in response to chronic injury, and subsequently contribute to liver regeneration. The mechanism underlying hepatocyte-to-ductal metaplasia has not been explored until now. In mouse models of liver fibrosis, a florid BEC response was observe...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2372-9
更新日期:2020-03-23 00:00:00