Abstract:
BACKGROUND:Reprogrammed energy metabolism has become an emerging hallmark of cancer in recent years. Transporters have been reported to be amino acid sensors involved in controlling mTOR recruitment and activation, which is crucial for the growth of both normal and tumor cells. L-type amino acid transporter 2 (LAT2), encoded by the SLC7A8 gene, is a Na+-independent neutral amino acid transporter and is responsible for transporting neutral amino acids, including glutamine, which can activate mTOR. Previous studies have shown that LAT2 was overexpressed in gemcitabine-resistant pancreatic cancer cells. However, the role of LAT2 in chemoresistance in pancreatic cancer remains uncertain and elusive. METHODS:The effects of LAT2 on biological behaviors were analyzed. LAT2 and LDHB levels in tissues were detected, and the clinical value was evaluated. RESULTS:We demonstrated that LAT2 emerged as an oncogenic protein and could decrease the gemcitabine sensitivity of pancreatic cancer cells in vitro and in vivo. The results of a survival analysis indicated that high expression levels of both LAT2 and LDHB predicted a poor prognosis in patients with pancreatic cancer. Furthermore, we found that LAT2 could promote proliferation, inhibit apoptosis, activate glycolysis and alter glutamine metabolism to activate mTOR in vitro and in vivo. Next, we found that gemcitabine combined with an mTOR inhibitor (RAD001) could reverse the decrease in chemosensitivity caused by LAT2 overexpression in pancreatic cancer cells. Mechanistically, we demonstrated that LAT2 could regulate two glutamine-dependent positive feedback loops (the LAT2/p-mTORSer2448 loop and the glutamine/p-mTORSer2448/glutamine synthetase loop) to promote glycolysis and decrease gemcitabine (GEM) sensitivity in pancreatic cancer. CONCLUSION:Taken together, our data reveal that LAT2 functions as an oncogenic protein and could regulate glutamine-dependent mTOR activation to promote glycolysis and decrease GEM sensitivity in pancreatic cancer. The LAT2-mTOR-LDHB pathway might be a promising therapeutic target in pancreatic cancer.
journal_name
J Exp Clin Cancer Resjournal_title
Journal of experimental & clinical cancer research : CRauthors
Feng M,Xiong G,Cao Z,Yang G,Zheng S,Qiu J,You L,Zheng L,Zhang T,Zhao Ydoi
10.1186/s13046-018-0947-4subject
Has Abstractpub_date
2018-11-12 00:00:00pages
274issue
1eissn
0392-9078issn
1756-9966pii
10.1186/s13046-018-0947-4journal_volume
37pub_type
杂志文章abstract:BACKGROUND:alpha-Methylacyl-CoA racemase (AMACR), an immunomarker for prostatic adenocarcinoma, has been shown to be expressed in a variety of other neoplasms. This study aims to evaluate immunohistochemical expression of the AMACR in neoplastic and nonneoplastic liver lesions, and assess its value in the diagnosis of ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-27-2
更新日期:2008-05-15 00:00:00
abstract:BACKGROUND:The aim of this retrospective study was to assess the results concerning the regional and systemic toxicity and complications in 242 chemo-hyperthermal treatments (HILPs) for lower limb melanoma. PATIENTS AND METHODS:60 HILPs (G-A) were performed with mild HT plus L-PAM (10 mg/lt) +/- D-actimomycin; 74 HILP...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-27-67
更新日期:2008-11-12 00:00:00
abstract::The aim of this study was to investigate serum levels of IL-2, IL-6 and IL-10 in the pretreatment period and to determine if high IL-2, IL-6, IL-10 levels correlate with the outcome in patients with Non-Hodgkin's Lymphoma (NHL) in the post treatment period. Forty-three patients with the diagnosis of aggressive NHL wer...
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::Primary lymphoma of the breast is a rare disease that has been estimated to represent from 0.05% to 0.53% of all malignant breast tumors and approximately 2.2% of all extranodal lymphomas. The aim of this study is to review all cases of primary lymphoma of the breast at the Institute of Oncology and Radiology of Serbi...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2000-06-01 00:00:00
abstract::Glioblastoma multiform (GBM) is the most common tumour of the central nervous system in humans. Unfortunately its prognosis is poor and because of the lack of efficacious therapies, immunotherapy is a potential treatment. Transfer factors (TF) are low molecular weight dialysable products extracted from immune cells wh...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2005-12-01 00:00:00
abstract::Increased expression of CD44 variants is often observed in differentiated thyroid carcinomas. To establish a method for gene diagnosis of thyroid without any additional invasions to the patients, RNA in leftover cells inside the needle used for fine needle aspiration biopsies (FNABs) was extracted to detect the expres...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1997-09-01 00:00:00
abstract:BACKGROUND:To investigate influencing factors of the metastatic lymph nodes ratio (MLR) and whether it is related to survival in patients with gastric adenocarcinoma. METHODS:We retrospectively evaluated the clinical features of 121 patients with gastric adenocarcinoma enrolled in our hospital between 2000 and 2007. T...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-28-55
更新日期:2009-04-26 00:00:00
abstract::Gastric cancer, characterized by poor prognosis, remains a global health problem. Thus, it is important to describe the biological factors which can affect the prognosis in this disorder. The aim of our study was the determination of the relationship between apoptotic index (AI) and other clinicopathological features ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
abstract::Colorectal cancer is the third most commonly diagnosed cancer worldwide. Although surgery remains the best treatment for this disease, adjuvant chemotherapy and radiotherapy are also very important in clinical practice. However, the notorious refractory lack of responses to radiochemotherapy greatly limits the applica...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-33-13
更新日期:2014-01-29 00:00:00
abstract:BACKGROUND:Classical Kaposi's Sarcoma (cKS) is a rare vascular tumor, which develops in subjects infected with Human Herpesvirus-8 (HHV-8). Beside the host predisposing factors, viral genetic variants might possibly be related to disease development. The aim of this study was to identify HHV-8 variants in patients with...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-014-0119-0
更新日期:2015-01-16 00:00:00
abstract:BACKGROUND:Dying cells after irradiation could promote the repopulation of surviving cancer cells leading to tumor recurrence. We aim to define the role of dying cells in promoting pancreatic cancer cells metastasis following radiotherapy. METHODS:Using the transwell system as the in vitro co-culture model, a small nu...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0726-2
更新日期:2018-04-03 00:00:00
abstract:BACKGROUND:Kindlin-2 is a member of the focal adhesion protein family that regulates invasion and metastasis in multiple malignancies; however, little is known about the role of Kindlin-2 in hepatocellular carcinoma (HCC) progression. METHODS:Immunohistochemistry was used to investigate Kindlin-2 expression in 177 pai...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0603-4
更新日期:2017-09-29 00:00:00
abstract::A study of laryngeal carcinomas was performed in order to analyze (a) the expression of p53/p21, cyclin D1/cyclin E, p21/p27 (b) the relation of normal and abnormal protein expression, with the proliferation status, as determined by the expression of Ki67 and PCNA and (c) the correlation of our findings with prognosis...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2005-09-01 00:00:00
abstract:BACKGROUND:Increased expression of epidermal growth factor receptor (EGFR) and its ligands is associated with poor prognosis and chemoresistance in many carcinoma types, but its role in head and neck squamous cell carcinoma (HNSCC) is unclear. Our aim was to clarify whether mRNA expression of EGFR-ligands was linked to...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0422-z
更新日期:2016-09-26 00:00:00
abstract:BACKGROUND:As the expression of human sperm protein 17 (Sp17) in normal tissue is limited and the function is obscure, its aberrant expression in malignant tumors makes it to be a candidated molecular marker for tumor imaging diagnosis and targeting therapy of the diseases.The aim of this research is to evaluate the ta...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-30-25
更新日期:2011-03-03 00:00:00
abstract:BACKGROUND:The chemokine receptors CXCR4 and CCR7 play an important role in cancer invasion and metastasis. This study investigated the expression of CXCR4, CCR7, CXCL12, CCL21, and EGFR to illustrate the role of these biomarkers in breast cancer metastasis and prognosis. METHODS:The CXCR4, CCR7, CXCL12, CCL21, and EG...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-29-16
更新日期:2010-02-24 00:00:00
abstract:BACKGROUND:This is a retrospective cross sectional study aimed to verify whether Multiplex Ligation-dependent Probe Amplification (MLPA), a quantitative molecular assay, may represent a valuable reflex test in breast cancer with equivocal HER2 expression by immunohistochemistry and HER2 gene signals/nucleus (s/n) rangi...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0613-2
更新日期:2017-10-13 00:00:00
abstract::The Editor-in-Chief has retracted this article [1] due to concerns about the figures. In Figure 3C, the images from the colony formation assays of all cell lines, excluding the control for the HCCLM9 cell line, contain identical patterns of colonies; this suggests that despite the fact they are supposed to be observat...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,撤回出版物
doi:10.1186/s13046-019-1224-x
更新日期:2019-05-23 00:00:00
abstract:BACKGROUND:Hippo/YAP pathway is known to be important for development, growth and organogenesis, and dysregulation of this pathway leads to tumor progression.We and others find that YAP is up-regulated in human gliomas and associated with worse prognosis of patients. However, the role and mechanism of YAP in glioma pro...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0606-1
更新日期:2017-09-29 00:00:00
abstract::Gastric tissue was transplanted from the fundic and pyloric mucosa of 8-week old female F344 rats into the duodenum of males. Autopsy, 12 months after the operation, revealed grafts associated with persistent stones in the duodenum and/or calcification in the tissue. Pepsinogen positive chimeric glands with goblet cel...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2000-06-01 00:00:00
abstract:BACKGROUND:Expression of the Sp1 transcription factor is induced by hypoxia, and the ADAM17 promoter contains predicted Sp1 binding sites. ADAM17 contributes to hypoxic-induce invasiveness of glioma. In this study, we investigated whether Sp1 transcription factor induces ADAM17 and/or contributes to tumor cell invasive...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-28-129
更新日期:2009-09-22 00:00:00
abstract::Cancer-associated fibroblasts (CAFs) plays an essential role in cancer cell growth, metabolism and immunoreaction. Autophagy is an intracellular self-degradative process that balances cell energy source and regulates tissue homeostasis. Targeting autophagy has gained interest with multiple preclinical and clinical tri...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/s13046-019-1172-5
更新日期:2019-04-23 00:00:00
abstract:BACKGROUND:Increased serum level of parathyroid hormone (PTH) was found in metastatic prostate cancers. Calcimimetic R-568 was reported to reduce PTH expression, to suppress cell proliferation and to induce apoptosis in parathyroid cells. In this study, we investigated the effect of R-568 on cellular survival of prosta...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-28-100
更新日期:2009-07-14 00:00:00
abstract:BACKGROUND:Localized C3 deposition is a well-known factor of inflammation. However, its role in oncoprogression of gastric cancer (GC) remains obscured. This study aims to explore the prognostic value of C3 deposition and to elucidate the mechanism of C3-related oncoprogression for GC. METHODS:From August to December ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 临床试验,杂志文章
doi:10.1186/s13046-019-1514-3
更新日期:2020-01-13 00:00:00
abstract::This study was conducted to establish a feasible intraperitoneal xenograft model in nude mice which mimicked the dynamic progression of human ovarian cancer and to explore its potential for preclinical trials. A human ovarian tumor line SKOV3 was originally injected s.c. to develop tumors; then the tumors were harvest...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2007-12-01 00:00:00
abstract:BACKGROUND AND AIM:in recent years, Livin, a new member of IAPs family, is found to be a key molecule in cancers. Researchers consider Livin may become a new target for tumor therapy; however, the role of it in bladder cancer is still unclear. The purpose of this article is to investigate Antisense Oligonucleotide (ASO...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-29-63
更新日期:2010-06-03 00:00:00
abstract:BACKGROUND:The prognosis of human astrocytoma is poor, and the molecular alterations underlying its pathogenesis still needed to be elucidated. Nucleolar and spindle associated protein 1 (NUSAP1) was observed in several types of cancers, but its role in astrocytoma remained unknown. METHODS:The expression of NUSAP1 in...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0597-y
更新日期:2017-09-12 00:00:00
abstract::Renal cell carcinoma, in a high percentage of patients, metastasizes early, sometimes mimicking other lesions. We present a case of an asymptomatic papillary renal cell carcinoma that presented neck metastases as the initial manifestation. The laterocervical and supraclavicular masses were considered consistent with n...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00
abstract:BACKGROUND:Colorectal cancer (CRC) arises as a consequence of genetic events such as gene mutation and epigenetic alteration. The aim of this study was to identify new hypermethylated candidate genes and methylation-based therapeutic targets using vincristine in CRC. METHODS:We analyzed the methylation status of 27,57...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-33-4
更新日期:2014-01-06 00:00:00
abstract::Doxorubicin (DOX) has a wide spectrum of antitumor activity with dose-related cardiotoxicity as a major side effect. This cardiotoxicity has been suggested to result from the generation of oxygen-free radicals. The objective of the present study was to investigate the influence of the antioxidant, thymoquinone (TQ) on...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00