Downregulation of LAT1 expression suppresses cholangiocarcinoma cell invasion and migration

Janpipatkul, Keatdamrong; Suksen, Kanoknetr; Borwornpinyo, Suparerk; Jearawiriyapaisarn, Natee; Hongeng, Suradej; Piyachaturawat, Pawinee; Chairoungdua, Arthit

doi:10.1016/j.cellsig.2014.04.002

Cited by 45 publications

(48 citation statements)

References 43 publications

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“…Recently, SLC7A5 is found to be essential in sustaining mTORC1 activity by transport glutamine out of the cells and amino acids into the cells (Nicklin et al, ). Conversely, silencing of SLC7A5 expression results in repression of mTOR activity in multiple cell types (Nicklin et al, ; Janpipatkul et al, ). Here, we show that Dex caused a downregulation of SLC7A5 expression and a decline of amino acids transport in BeWo cells.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that LAT1 plays an important role in amino acid transport and placental cell proliferation (Kanai et al, 1998;Ritchie and Taylor, 2001;Chrostowski et al, 2010). Furthermore, SLC7A5 has been found to be critical for cancer cell proliferation (Fuchs and Bode, 2005;Fan et al, 2010;Elorza et al, 2012;Janpipatkul et al, 2014). However, little is known to date regarding whether and how SLC7A5 plays a role in the regulation of placental cell proliferation in response to synthetic GCs.…”

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confidence: 99%

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Dexamethasone Downregulates SLC7A5 Expression and Promotes Cell Cycle Arrest, Autophagy and Apoptosis in BeWo Cells

Zhang

2015

Journal Cellular Physiology

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Synthetic glucocorticoids (GCs) such as dexamethasone (Dex) are widely given to pregnant women to induce maturation and improve viability of preterm infants. Despite the beneficial effects, synthetic GCs have adverse effects on placental growth and nutrient transport system. However, the molecular mechanisms involved in these events remain unknown. Here we use a human placental choriocarcinoma cell line (BeWo) as model to explore the pathway linking amino acids transport with cell viability under Dex challenge. BeWo cells treated with Dex (100 nM) for 24 h demonstrated G1/S cell cycle arrest together with enhanced autophagy and apoptosis. Concurrently, the amino acid carrier SLC7A5 was down-regulated in association with impaired cellular amino acids uptake and inhibition of mammalian target of rapamycin (mTOR) signaling. Similar cellular responses were observed in BeWo cells treated with BCH, a classical System L inhibitor which inactivates SLC7A5. The glucocorticoid receptor (GR) antagonist RU486 was able to diminish Dex-induced translocation of GR into nucleus and to abolish these effects. Furthermore, Dex treatment significantly promoted the binding of GR to the proximal promoter sequence of SLC7A5 gene. Taken together, our results show that Dex downregulates SLC7A5 expression via GR-mediated transrepression. The impaired amino acids uptake leads to inhibition of mTOR signaling which in turn causes inhibited proliferation and enhanced autophagy and apoptosis in BeWo cells. These findings indicate that SLC7A5 mediates the effect of Dex on cell viability, thus providing a novel molecular target for the prevention and treatment of Dex-induced cell cycle arrest and apoptosis in placental cells.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Dexamethasone Downregulates SLC7A5 Expression and Promotes Cell Cycle Arrest, Autophagy and Apoptosis in BeWo Cells

Zhang

2015

Journal Cellular Physiology

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“…Up-regulations of LAT1 and 4F2hc that fasten formation of solid tumors were detected in several cancer cell lines including CCA cells [31,32]. Tumor associated calcium signal transducer 2 protein stimulated several human cancer growth and up-regulation of this protein was associated with poor prognosis particularly in invasive cancers [33].…”

Section: Accepted Manuscriptmentioning

confidence: 98%

Proteomics profiling of cholangiocarcinoma exosomes: A potential role of oncogenic protein transferring in cancer progression

Dutta

Reamtong

Panvongsa

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Cholangiocarcinoma (CCA), a common primary malignant tumor of bile duct epithelia, is highly prevalent in Asian countries and unresponsive to chemotherapeutic drugs. Thus, a newly recognized biological entity for early diagnosis and treatment is highly needed. Exosomes are small membrane bound vesicles found in body fluids and released by most cell types including cancer cells. The vesicles contain specific subset of proteins and nucleic acids corresponding to cell types and play essential roles in pathophysiological processes. The present study aimed to assess the protein profiles of CCA-derived exosomes and their potential roles. We have isolated exosomes from CCA cells namely KKU-M213 and KKU-100 derived from Thai patients and their roles were investigated by incubation with normal human cholangiocyte (H69) cells. Exosomes were internalized into H69 cells and had no effects on viability or proliferation of the host cells. Interestingly, the exosomes from KKU-M213 cells only induced migration and invasion of H69 cells. Proteomic analysis of the exosomes from KKU-M213 cells disclosed multiple cancer related proteins that are not present in H69 exosomes. Consistent with the protein profile, treatment with KKU-M213 exosomes induced β-catenin and reduced E-cadherin expressions in H69 cells. Collectively, our results suggest that a direct cell-to-cell transfer of oncogenic proteins via exosomal pathway may be a novel mechanism for CCA progression and metastasis.

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“…MiR-7 also plays a role in other digestive tract malignancies such as cholangiocarcinoma and ESCC [29,41] . However, the expression and exact role of miR-7 in these two malignancies need to be verified.…”

Section: Other Digestive Malignanciesmentioning

confidence: 99%

Role of microRNA-7 in digestive system malignancy

Chen¹

2016

WJGO

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There are several malignancies of the digestive system (including gastric, pancreatic and colorectal cancers, and hepatocellular carcinoma), which are the most common types of cancer and a major cause of death worldwide. MicroRNA (miR)-7 is abundant in the pancreas, playing an important role in pancreatic development and endocrine function. Expression of miR-7 is downregulated in digestive system malignancies compared with normal tissue. Although there are contrasting results for miR-7 expression, almost all research reveals that miR-7 is a tumor suppressor, by targeting various genes in specific pathways. Moreover, miR-7 can target different genes simultaneously in different malignancies of the digestive system. By acting on many cytokines, miR-7 is also involved in many gastrointestinal inflammatory diseases as a significant carcinogenic factor. Consequently, miR-7 might be a biomarker or therapeutic target gene in digestive system malignancies.

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Downregulation of LAT1 expression suppresses cholangiocarcinoma cell invasion and migration

Cited by 45 publications

References 43 publications

Dexamethasone Downregulates SLC7A5 Expression and Promotes Cell Cycle Arrest, Autophagy and Apoptosis in BeWo Cells

Dexamethasone Downregulates SLC7A5 Expression and Promotes Cell Cycle Arrest, Autophagy and Apoptosis in BeWo Cells

Proteomics profiling of cholangiocarcinoma exosomes: A potential role of oncogenic protein transferring in cancer progression

Role of microRNA-7 in digestive system malignancy

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