Abstract:
BACKGROUND:Glucose-6-phospate dehydrogenase (G6PD) is the limiting enzyme of the pentose phosphate pathway (PPP) correlated to cancer progression and drug resistance. We previously showed that G6PD inhibition leads to Endoplasmic Reticulum (ER) stress often associated to autophagy deregulation. The latter can be induced by target-based agents such as Lapatinib, an anti-HER2 tyrosine kinase inhibitor (TKI) largely used in breast cancer treatment. METHODS:Here we investigate whether G6PD inhibition causes autophagy alteration, which can potentiate Lapatinib effect on cancer cells. Immunofluorescence and flow cytometry for LC3B and lysosomes tracker were used to study autophagy in cells treated with lapatinib and/or G6PD inhibitors (polydatin). Immunoblots for LC3B and p62 were performed to confirm autophagy flux analyses together with puncta and colocalization studies. We generated a cell line overexpressing G6PD and performed synergism studies on cell growth inhibition induced by Lapatinib and Polydatin using the median effect by Chou-Talay. Synergism studies were additionally validated with apoptosis analysis by annexin V/PI staining in the presence or absence of autophagy blockers. RESULTS:We found that the inhibition of G6PD induced endoplasmic reticulum stress, which was responsible for the deregulation of autophagy flux. Indeed, G6PD blockade caused a consistent increase of autophagosomes formation independently from mTOR status. Cells engineered to overexpress G6PD became resilient to autophagy and resistant to lapatinib. On the other hand, G6PD inhibition synergistically increased lapatinib-induced cytotoxic effect on cancer cells, while autophagy blockade abolished this effect. Finally, in silico studies showed a significant correlation between G6PD expression and tumour relapse/resistance in patients. CONCLUSIONS:These results point out that autophagy and PPP are crucial players in TKI resistance, and highlight a peculiar vulnerability of breast cancer cells, where impairment of metabolic pathways and autophagy could be used to reinforce TKI efficacy in cancer treatment.
journal_name
J Exp Clin Cancer Resjournal_title
Journal of experimental & clinical cancer research : CRauthors
Mele L,la Noce M,Paino F,Regad T,Wagner S,Liccardo D,Papaccio G,Lombardi A,Caraglia M,Tirino V,Desiderio V,Papaccio Fdoi
10.1186/s13046-019-1164-5subject
Has Abstractpub_date
2019-04-12 00:00:00pages
160issue
1eissn
0392-9078issn
1756-9966pii
10.1186/s13046-019-1164-5journal_volume
38pub_type
杂志文章abstract::Arsenic trioxide has shown substantial efficacy in treating patients with relapsed or refractory acute promyelocytic leukemia (APL) as well as solid tumors. Arsenic can act through a considerable number of different pathways including mitochondrial respiration and tubulin formation, affecting growth, blood flow, diffe...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2004-06-01 00:00:00
abstract:BACKGROUND:Immunocytochemistry and RT-PCR have been widely used for the detection of circulating tumor cells in patients with breast cancer but their specificity is limited. Our purpose is to utilize a convenient and specific technology to detect circulating tumor cells in breast cancer patients. METHODS:To determine ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-28-57
更新日期:2009-04-28 00:00:00
abstract:BACKGROUND:Osteosarcoma (OS) is a high-grade bone sarcoma with early metastasis potential, and the clinical chemotherapy drugs that are currently used for its treatment have some limitations. Recently, several studies have reported the selective antitumor effect of oleandrin on various tumor cells. In this study, we ai...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-015-0232-8
更新日期:2015-10-06 00:00:00
abstract:BACKGROUND:Colon cancer represents one of the leading causes of gastrointestinal tumors in industrialized countries, and its incidence appears to be increasing at an alarming rate. Accumulating evidence has unveiled the contributory roles of cancer stem cells (CSCs) in tumorigenicity, recurrence, and metastases. The fu...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-020-01704-w
更新日期:2020-10-28 00:00:00
abstract::Axillary lymphadenectomy is a very important procedure in the staging of breast cancer patients. However, it is associated with a significant morbidity rate. On the other hand, using early diagnosis we can see a high number of cases where the lymph nodes are negatives. With the intention of avoiding unnecessary axilla...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00
abstract:BACKGROUND:Metastasis in breast cancer is a vital concern in treatment because most women with primary breast cancer have micrometastases to distant sites at diagnosis. As a member of the inhibitor of apoptosis protein (IAP) family, survivin has been proposed as an attractive target for new anticancer interventions. In...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-27-46
更新日期:2008-09-25 00:00:00
abstract:BACKGROUND:Lung cancer has long been the most dangerous malignant tumor among males in both well developed and poorly developed countries. Radiotherapy plays a critical role in the curative management of inoperable non-small cell lung cancer (NSCLC) and is also used as a post-surgical treatment in lung cancer patients....
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0285-3
更新日期:2016-01-12 00:00:00
abstract:BACKGROUND:Colon cancer is the second leading cancer worldwide. Recurrent disease and chemotherapeutic drug resistance are very common in the advanced stage of colon cancer. ATP-citrate lyase (ACLY), the first-step rate-controlling enzyme in lipid synthesis, is elevated in colon cancer. However, it remains unclear abou...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1391-9
更新日期:2019-09-12 00:00:00
abstract:BACKGROUND:Manganese superoxide dismutase (MnSOD) upregulating FoxM1 have previously been demonstrated promoting lung cancer stemness. Isovitexin exhibits antitumor activities in various cancers. This study aimed to assess whether isovitexin inhibits hepatic carcinoma stem-like cells (HCSLCs) features via regulating Mn...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1244-6
更新日期:2019-06-17 00:00:00
abstract::Screening for ovarian cancer is an important step in improving ovarian cancer mortality. This is a report of screening for ovarian cancer using transvaginal sonography (TVS) on 2,095 asymptomatic women during the past four years. Ovarian tumors over 30 mm in diameter were detected in 87 women (4.2%). Fourteen tumors w...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1997-06-01 00:00:00
abstract::Two-year protocols are commonly used for long-term assay of chemicals for carcinogenicity. However, in some cases, if animals have been exposed to tested agent from the young age and sacrificed at the age of 2, an underestimation of the carcinogenic potential of non-genotoxic agents and tumor promoters is possible. Da...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:
更新日期:1998-09-01 00:00:00
abstract:BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous cancer in which differences in survival rates might be related to a variety in gene expression profiles. Although the molecular biology of PDAC begins to be revealed, genes or pathways that specifically drive tumour progression or metastasis are not ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-31-68
更新日期:2012-08-27 00:00:00
abstract:BACKGROUND:The oncogenic activity of the high risk human papillomavirus type 16 (HPV16) is fully dependent on the E6 and E7 viral oncoproteins produced during viral infection. The oncoproteins interfere with cellular homeostasis by promoting proliferation, inhibiting apoptosis and blocking epithelial differentiation, d...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-021-01841-w
更新日期:2021-01-23 00:00:00
abstract:BACKGROUND:Novel therapies tailored to the molecular composition of esophageal squamous cell carcinoma (ESCC) are needed to improve patient survival. We investigated the regulatory network of long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) and sex-determining region Y-box 9 (SOX9), and the...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0658-2
更新日期:2017-12-13 00:00:00
abstract::PD-1/PD-L1 checkpoint blockades have achieved significant progress in several kinds of tumours. Pembrolizumab, which targets PD-1, has been approved as a first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with positive PD-L1 expression. However, PD-1/PD-L1 checkpoint blockades have not achie...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/s13046-019-1085-3
更新日期:2019-02-18 00:00:00
abstract:BACKGROUND:Anti-angiogenesis remains an attractive strategy for cancer therapy. Some anti-angiogenic reagents have bell-shape dose-response curves with higher than the effective doses yielding lower anti-angiogenic effects. In this study, two different types of anti-angiogenic reagents, a receptor tyrosine kinase inhib...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,收录出版
doi:10.1186/s13046-019-1324-7
更新日期:2019-08-28 00:00:00
abstract:BACKGROUND:Progranulin (PGRN), as a multifunctional growth factor, is overexpressed in multiple tumors, but the role of PGRN on tumor immunity is still unclear. Here, we studied the effect of PGRN on breast cancer tumor immunity and its possible molecular mechanism. METHODS:The changes of macrophage phenotypes after P...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-020-01786-6
更新日期:2021-01-04 00:00:00
abstract::Cancer vaccine therapy represents a promising therapeutical option. Consistently, with these new treatment strategies, the use of dendritic cell vaccines is becoming increasingly widespread and currently in the forefront for cancer treatment. The purpose of this study was to evaluate the feasibility and safety of tumo...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2007-06-01 00:00:00
abstract::Proliferative activity in 78 glioma specimens was assessed immunohistochemically by determining proliferating index of tumor cells (PTC-PI) and endothelial cells (PEC-PI) using the MIB-1 monoclonal antibody. The PTC-PI of anaplastic astrocytoma (9.0 +/- 5.8: mean + standard deviation) was significantly higher than tha...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1997-06-01 00:00:00
abstract::In the original publication of this manuscript [1], Fig. 5E lower panel was incorrect due to an error in the preparation of these figures for publication. It was noticed that in the lower panel of Fig. 5E, one mouse image of ApoE-/- + PBS group (upper) was a photograph coming from ApoE-/- + BAPN pre-treatment group (l...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 已发布勘误
doi:10.1186/s13046-019-1422-6
更新日期:2019-10-15 00:00:00
abstract::The mutational spectrum of p53 gene and the biological effects of mutant p53 protein vary greatly from one type of tumor to another. To investigate the biological effects of mutant p53 gene in human lung adenocarcinoma, mutant p53 was silenced by RNA interference (RNAi) in cell line Anip973. Then, the effects of mutan...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND:Head and neck cancer (HNC) is one of the most common deadly diseases worldwide. An increasing number of studies have recently focused on the malignant functions of cancer-associated fibroblasts (CAFs) in numerous cancers. However, the underlying mechanisms by which CAF-derived exosomes promote tumor progress...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1144-9
更新日期:2019-04-08 00:00:00
abstract:BACKGROUND:To determine whether early monitoring of the effects of bevacizumab in patients with recurrent high-grade gliomas, by a Perfusion Computed Tomography (PCT), may be a predictor of the response to treatment assessed through conventional MRI follow-up. METHODS:Sixteen patients were enrolled in the present stud...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 临床试验,杂志文章
doi:10.1186/1756-9966-31-33
更新日期:2012-04-11 00:00:00
abstract:BACKGROUND:There is no consensus regarding the secondary cytoreduction surgery (CRS) in recurrent ovarian cancer patients. The present study aims to determine the value of secondary CRS and the eligible subgroup for this procedure. METHODS:96 platinum-sensitive recurrent ovarian cancer patients were recruited from Jia...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-32-61
更新日期:2013-09-02 00:00:00
abstract:BACKGROUND:Glioblastoma multiforme is a CNS cancer characterized by diffuse infiltrative growth, aggressive clinical behavior and very poor prognosis. The state-of-art clinical approach to this disease consists of surgical resection followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide. T...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 社论
doi:10.1186/s13046-020-1534-z
更新日期:2020-01-31 00:00:00
abstract::Glutathione S-transferases (GSTs) are a group of enzymes involved in the detoxification process of carcinogens and other substances. The genes encoding isoenzymes M1 and T1 have "null" alleles, which are polymorphic in humans. Our purpose was to examine whether the GSTM1 and GSTT1 homozygous null genotypes have an imp...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2004-09-01 00:00:00
abstract::In a family consisting of 48 persons with high predisposition to familial stomach cancer (SCr), SCr was diagnosed in 8 persons (I-2; II-1,3,4; III-1,2,3,4). Moreover, one woman (III-8) had bilateral breast cancer and two (proband: IV-1 and her father's cousin: III-10) chronic gastritis. The proband, her father's cousi...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1997-12-01 00:00:00
abstract::Tumours involving the scrotum are rare and primary malignant melanoma is among the rarest of these lesions. Between 1949 and 1996 only 7 cases have been reported. We present two cases of scrotal melanoma. The current recommendations and management strategies are discussed on the basis of a review of the literature. ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:
更新日期:1998-03-01 00:00:00
abstract:BACKGROUND:Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. MicroRNAs (miRNAs) have been indicated as crucial actors in cancer biology. Accumulating evidence suggests that miRNAs can be used as diagnostic and prognostic markers for NSCLC. METHODS:The purpose of this study was to characterize a...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0882-4
更新日期:2018-09-18 00:00:00
abstract::A single guanine insertion (1G/2G polymorphism) in the promoter of the matrix metalloproteinase (MMP-1) gene creates a binding site for the transcription factor and may affect the level of transcription of MMP-1. An elevated level of MMP-1 in cancer cells may facilitate their invasion and contribute to metastasis. To ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00