Abstract：
:Cancer stem cells (CSC) are critical for initiation, metastasis, and relapse of cancers, however, the underlying mechanism governing stemness of CSC remains unknown. Herein, we have investigated the roles of phosphodiesterase 5 (PDE5) in stemness of prostate cancer cells. Both PDE5 and WW domain-containing transcription regulator protein-1 (TAZ), a core effector of Hippo pathway, are highly expressed in the PC3-derived cancer stem cells (PCSC). Either TAZ knockdown or inhibition of PDE5 activity attenuated colony formation, altered expression patterns of stem cell markers, and enhanced cisplatin cytotoxicity, resulting in attenuation of stemness in PCSC. In addition, inhibition of PDE5 activity by its specific inhibitors activates cGMP-dependent protein kinase G (PKG), which in turn induces MST/LATS kinases, resulting in cytosolic degradation of TAZ and activation of Hippo pathway. Accordingly, knockdown of TAZ almost completely abolished PDE5 inhibitor-induced attenuation in stemness in cultured PCSC, whereas knockdown of TAZ not only abolished PDE5 inhibitor-induced attenuation in stemness but also facilitated PDE5 inhibitor-induced trans-differentiation in PCSC xenografts. Together, the present study has uncovered that PDE/cGMP/PKG signal targets to Hippo/TAZ pathway in maintaining stemness of PCSC, and suggested that PDE5 inhibitors in combination with chemotherapeutic agents could effectively prevent initiation, metastasis, and relapse of prostate cancer.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Liu N,Mei L,Fan X,Tang C,Ji X,Hu X,Shi W,Qian Y,Hussain M,Wu J,Wang C,Lin S,Wu Xdoi
10.1016/j.canlet.2016.05.010subject
Has Abstractpub_date
2016-08-01 00:00:00pages
38-50issue
1eissn
0304-3835issn
1872-7980pii
S0304-3835(16)30305-6journal_volume
378pub_type
杂志文章相关文献
CANCER LETTERS文献大全abstract：:The concept of metronomic chemotherapy (MC) has evolved from a descriptive preclinical phenomenon encompassing inhibition of angiogenesis to a clinically validated treatment concept involving multiple potential mechanisms of action. Clinicians are progressively more incline to consider MC as a component of mainstream ...
journal_title：Cancer letters
pub_type： 杂志文章,评审
doi：10.1016/j.canlet.2016.12.041
更新日期：2017-08-01 00:00:00
abstract：:Epidemiological reports suggest that Asians consuming a diet high in soy have a low incidence of clinically manifested prostate cancer. We have tested the hypothesis that life-time exposure to genistein, the primary isoflavone component of soy, is responsible for this protective effect. Lobund-Wistar rats were exposed...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/s0304-3835(01)00811-4
更新日期：2002-12-01 00:00:00
abstract：:Pancreatic expression of the p53 tumor suppressor gene was studied in pancreatic adenocarcinomas and chronic pancreatitis. By immunohistochemistry, 16 of 34 (47%) cancers and none of the 24 chronic pancreatitis samples revealed nuclear staining. Sequence analysis indicated that 8 of 24 (33%) cancers were mutated for t...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/0304-3835(93)90168-9
更新日期：1993-05-14 00:00:00
abstract：:The current standard approach for assessing carcinogenic potential is to conduct a near lifetime rodent pathology study with the high dose set to the maximum tolerated dose (MTD) of the test chemical. The linearized multistage model is then used as the default approach to estimate the potential human cancer risk at en...
journal_title：Cancer letters
pub_type： 杂志文章,评审
doi：10.1016/0304-3835(95)03794-W
更新日期：1995-06-29 00:00:00
abstract：:The study describes the kinetics of demethylation of mononitrosocaffeidine (MNC), a new asymmetric N-nitrosamine derived from caffeine. The demethylation of its precursor compound caffeidine was also studied. The results presented here suggest (a) that liver microsomes from fasted rats preferentially demethylate the N...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/0304-3835(94)90071-x
更新日期：1994-04-29 00:00:00
abstract：:The activity of cancer procoagulant (CP), prothrombin time (PT), activated partial thromboplastin time (APTT), the concentration of thrombin-antithrombin complexes (TAT) and the concentration of fibrinogen were analysed in blood of breast cancer patients scheduled for surgery. The serum level of CP activity was depend...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/s0304-3835(99)00230-x
更新日期：1999-11-01 00:00:00
abstract：:Artemisinin, a compound isolated from the sweet wormwood Artemisia annua L., has previously been shown to have selective toxicity towards cancer cells in vitro. In the present experiment, we studied the potential of artemisinin to prevent breast cancer development in rats treated with a single oral dose (50mg/kg) of 7...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2005.01.019
更新日期：2006-01-08 00:00:00
abstract：:Tumor-derived exosomes (TEXs) contain enriched miRNAs that act as novel non-invasive biomarkers for cancer diagnosis and play a role in cancer progression. We investigated the exosomal miRNAs that affect cancer progression in non-small cell lung cancer (NSCLC) and identified the specific molecules involved. We identif...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2020.01.023
更新日期：2020-04-10 00:00:00
abstract：:Homeobox genes, involved in embryonic development and tissues homeostasis in adults, are often deregulated in cancer, but their relevance in pathology is far from being fully elucidated. In colon cancers, we report that the homeoproteins HoxB7 and Cdx2 exhibit different heterogeneous patterns, Cdx2 being localized in ...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2016.02.026
更新日期：2016-05-01 00:00:00
abstract：:Pancreatic cancer has a poor prognosis, even with surgery. ING4 is a member of the inhibitor of growth (ING) tumor suppressor family that has potent inhibitory effects on a variety of tumors; meanwhile, radiotherapy is a common adjunctive therapy for pancreatic cancer. Prior to this study, the effectiveness of a combi...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2011.11.003
更新日期：2012-03-28 00:00:00
abstract：:Artesunate (ART), a semi-synthetic derivative of artemisinin extracted from the Chinese herb Artemisia annua, is a safe and effective antimalarial drug. ART has now been analyzed for its anti-angiogenic activity in vivo and in vitro. The anti-angiogenic effect in vivo was evaluated on chicken chorioallantoic membrane ...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2004.03.014
更新日期：2004-08-10 00:00:00
abstract：:The effect of diethylstilbestrol propionate (DES; 1 mg/kg body wt. was studied in the female offspring of rats exposed subcutaneously on the 19th day of gestation. Examination of vaginal smears showed persistent estrus in adult rats treated prenatally with DES. Compensatory ovarian hypertrophy (COH) induced by hemicas...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/s0304-3835(79)80008-7
更新日期：1979-02-01 00:00:00
abstract：:Cancer results from genetic alterations in intracellular signaling pathways, which normally orchestrate the execution of developmental programs and the organismic response to extrinsic factors. Mutations in upstream activators and components of the cytoplasmic (Ras-Raf MEK-ERK) cascade frequently occur in tumors. In v...
journal_title：Cancer letters
pub_type： 杂志文章,评审
doi：10.1016/j.canlet.2004.08.003
更新日期：2005-01-10 00:00:00
abstract：:Despite the improved 5-year survival rate of breast cancer, triple-negative breast cancer (TNBC) remains a challenge due to lack of effective targeted therapy and higher recurrence and metastasis than other subtypes. To identify novel druggable targets and to understand its unique biology, we tried to implement 24 pat...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2018.04.020
更新日期：2018-08-01 00:00:00
abstract：:The candidate prostate cancer gene ELAC2 encodes tRNA 3' processing endoribonuclease (tRNase ZL). We produced recombinant human tRNase ZL's, which contain one to three amino-acid substitutions from three missense mutations (Ser217Leu, Ala541Thr, and Arg781His) that are associated with the occurrence of prostate cancer...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2004.09.013
更新日期：2005-05-26 00:00:00
abstract：:The constitutional expression of heat shock proteins (HSP) 27, 70 and 90 in human breast, colon and ovarian cancer cells transplanted into severe combined immunodeficient (SCID) mice was evaluated. In addition their induced expression under chemotherapeutic stress was analyzed. The oestrogen receptor positive breast c...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/s0304-3835(00)00601-7
更新日期：2000-12-08 00:00:00
abstract：:Macrophages that infiltrate tumor tissues, or tumor-associated macrophages (TAMs), affect the malignant behaviors of tumor cells. In this study, we attempted to induce monocytes to differentiate into TAM-like cells producing matrix metalloproteinases (MMPs) by co-culture with tumor cells. When human monocytes were co-...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2011.09.029
更新日期：2012-02-28 00:00:00
abstract：:Hepatocellular carcinoma (HCC) is heterogeneous, rendering its current curative treatments ineffective. The emergence of single-cell genomics represents a powerful strategy in delineating the complex molecular landscapes of cancers. In this study, we demonstrated the feasibility and merit of using single-cell RNA sequ...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2019.06.002
更新日期：2019-09-10 00:00:00
abstract：:Many studies have shown that the activation of beta-catenin signaling can promote oncogenesis, and it is therefore of interest to find agents that modulate this pathway. Recent work has shown using B lymphoma cells that infection by Epstein-Barr virus (EBV) and expression of its latent membrane protein (LMP)-1, cause ...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2008.10.041
更新日期：2009-04-18 00:00:00
abstract：:Malignant tumors remain a major health burden throughout the world, and effective therapeutic strategies are urgently needed. Combining gene therapy with chemotherapeutics in a single delivery system is more effective than co-treatment of cancer with individual delivery systems carrying either gene or drug. In this st...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2015.01.011
更新日期：2015-04-10 00:00:00
abstract：:A novel second generation retroviral producer cell strategy (an adenoviral/retroviral combined delivery system) has been developed by this laboratory. In the present studies, this delivery system was used to examine its delivery efficiency in vitro and in vivo by using a marker gene, LacZ, and a therapeutic gene, herp...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/s0304-3835(02)00241-0
更新日期：2002-10-28 00:00:00
abstract：:Tocopherol, a well known tissue anti-oxidant, given before local X-ray irradiation of 2 transplantable rat tumours was previously found to increase significantly the effect of irradiation. In the present study tocopherol did not influence the development of tumour necroses during growth of a transplantable rat hepatom...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/s0304-3835(78)80037-8
更新日期：1978-10-01 00:00:00
abstract：:The pharmacological specificity of adrenergic receptors in the plasma membrane of rat ascites hepatoma AH130 cells was compared with that in normal rat hepatocytes. The number of [125I]iodocyanopindolol-binding sites was much greater in AH130 cells than in the hepatocytes. We characterized the alpha-adrenergic recepto...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/0304-3835(88)90069-9
更新日期：1988-04-01 00:00:00
abstract：:Cancer is a multistep process that arises from a series of genetic and epigenetic events. With recent technological advances there has been a burst in genome sequencing and epigenetic studies revealing a plethora of alterations that may contribute to cancer. However, the great challenge for the cancer research communi...
journal_title：Cancer letters
pub_type： 杂志文章,评审
doi：10.1016/j.canlet.2016.03.029
更新日期：2017-02-28 00:00:00
abstract：:Innate resistance to various therapeutic interventions is a hallmark of cancer. In recent years, however, acquired resistance has emerged as a daunting challenge to anticancer treatments including chemotherapy, radiation and targeted therapy, which abolishes the efficacy of otherwise successful regimens. Cancer cells ...
journal_title：Cancer letters
pub_type： 杂志文章,评审
doi：10.1016/j.canlet.2015.07.044
更新日期：2016-09-28 00:00:00
abstract：:alpha-Toxin (alpha-hemolysin) of Staphylococcus aureus is a pore-forming bacterial toxin which after caveolin-1-dependent assembly induces apoptosis in eukaryotic cells. We investigated if a sub-toxic concentration of staphylococcal alpha-toxin could enhance cisplatin-induced apoptosis and overcome acquired cisplatin-...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2008.02.007
更新日期：2008-06-28 00:00:00
abstract：:The p53 signaling pathway plays critical roles in determining the radio-sensitivity of normal tissues but is frequently inactivated in cancer. In various cancer cells, p53 has different effects on radio-sensitivity through complex mechanisms. Acetylation of p53 is an important means of post-translational modifications...
journal_title：Cancer letters
pub_type： 杂志文章,评审
doi：10.1016/j.canlet.2015.04.015
更新日期：2015-07-28 00:00:00
abstract：:Mouse mammary tumor viruses (MMTV) replicate in the mammary gland, appear as infectious particles in mother's milk and invade the sucking pups from the intestinal tract. The immune system is essential for MMTV in the gut to reach the mammary gland. These properties make the life cycle of MMTV unique. We review the onc...
journal_title：Cancer letters
pub_type： 杂志文章,评审
doi：10.1016/0304-3835(94)03671-5
更新日期：1995-03-23 00:00:00
abstract：:Costunolide, the predominant sesquiterpene lactone in Saussureae radix, has been reported to exhibit potent chemopreventive effects on carcinogenesis. Effects of costunolide on cellular activation induced by a tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) were investigated using a reporter g...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/s0304-3835(00)00704-7
更新日期：2001-03-10 00:00:00
abstract：:Angiogenesis remains a sensible target for pancreatic ductal adenocarcinoma (PDAC) therapy. VEGF, PDGF, FGF and their receptors are expressed at high levels and correlate with poor prognosis in human PDAC. Nintedanib is a triple angiokinase inhibitor that targets VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β signaling. We invest...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2014.12.027
更新日期：2015-03-01 00:00:00
