Expression of L-type amino acid transporter 1 (LAT1) in neuroendocrine tumors of the lung

Kaira, Kyoichi; Oriuchi, Noboru; Imai, Hisao; Shimizu, Kimihiro; Yanagitani, Noriko; Sunaga, Noriaki; Hisada, Takeshi; Kawashima, Osamu; Iijima, Hironobu; Ishizuka, Tamotsu; Kanai, Yoshikatsu; Endou, Hitoshi; Nakajima, Takashi; Mori, Masatomo

doi:10.1016/j.prp.2008.02.003

Cited by 57 publications

(63 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, with the exception of SLC7A5, none of the validated or doubly-predicted target genes are known to be overexpressed in SCLC cell lines or tumors [11]. SLC7A5 protein overexpression in SCLC is in accordance with the previously described downregulation of miR-126 expression.…”

Section: Overexpression Of Mir-126 Suppresses Slc7a5 Expression At Bosupporting

confidence: 73%

miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

Margitai²,

et al. 2011

View full text Add to dashboard Cite

Edited by Tamas Dalmay Keywords:Small cell lung cancer miR-126 SLC7A5 G1 delay a b s t r a c t Despite intensive efforts to improve therapies, small cell lung cancer (SCLC) still has a dismal median survival of 18 months. Since miR-126 is under-expressed in the majority of SCLC tumors, we investigated the effect of miR-126 overexpression on the proliferation and cell cycle distribution of H69 cells. Our results demonstrate that miR-126 inhibits proliferation of H69 cells, by delaying the cells in the G1 phase. Short interfering RNA (siRNA) mediated suppression of SLC7A5, a predicted target of mir-126, has the same effect on H69 cells. We also show for the first time that SLC7A5 is a direct target of miR-126.

show abstract

Section: Overexpression Of Mir-126 Suppresses Slc7a5 Expression At Bosupporting

confidence: 73%

miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

Margitai²,

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Furthermore, this transporter is upregulated in a wide range of malignant cells (15). LAT1 expression is associated with poor prognosis (16)(17)(18) as well as metastases and angiogenesis (19). Because of its high expression in neuroendocrine malignancies, LAT1 is unlikely to be satiated, which is in accordance with the results of the accumulation experiment of 18 F-DOPA after treatment with the specific inhibitor of LAT: BCH led to a decrease of the same extent in both 18 F-DOPA-H and 18 F-DOPA-L.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Biodistribution of No-Carrier-Added 6-¹⁸F-Fluoro-3,4-Dihydroxy-l-Phenylalanine (¹⁸F-DOPA), Produced by a New Nucleophilic Substitution Approach, Compared with Carrier-Added ¹⁸F-DOPA, Prepared by Conventional Electrophilic Substitution

et al. 2014

View full text Add to dashboard Cite

“…These tumors are represented by a wide range of pathological entities (1)(2)(3)(4)(5). It is now widely recognized that NE tumors of the lung include a spectrum that ranges from low-grade typical carcinoid (TC) and intermediate-grade atypical carcinoid (AC) to high-grade large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinomas (SCLC) (1)(2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

“…It was first identified on the cell surface of T lymphocytes (5). However, 4F2hc has been shown to be involved in the cellular proliferation, transformation, fusion, and adhesion and also in the L-type amino acid transport (LAT) system, in addition to regulating integrin activation, and therefore, integrin signaling and anchorage-independent growth.…”

Section: Introductionmentioning

confidence: 99%

“…This demand is increased by the availability of nutrients through vascular formation and enhanced by cellular entry of nutrients through up-regulation of specific transporters. Cancer cells enhance glucose uptake via induction of glucose transporter 1 (Glut1) and Glut3, and meet their amino acid demands by induction of the L-type amino acid transporter 1 (LAT1) (15,16 3 Pathology, and (16), and a positive LAT1 expression has been described to be correlated with the grade of neuroendocrine tumors of the lung (5). A recent study suggests that 4F2hc stabilizes Glut1 protein and contributes to the regulation not only of amino acids, but also of glucose metabolism (17).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Expression of 4F2hc (CD98) in pulmonary neuroendocrine tumors

Kaira

Ohde²,

Endo³

et al. 2011

Oncol Rep

Self Cite

View full text Add to dashboard Cite

Abstract. 4F2hc (CD98) has been associated with tumor growth, and is highly expressed in various tumors. The aim of this study was to evaluate the clinicopathological significance of 4F2hc expression in pulmonary neuroendocrine (NE) tumors. Surgically-resected patient tumors including 16 large cell neuroendocrine carcinoma (LCNEC), 12 small cell lung cancer (SCLC), 1 atypical carcinoid (AC) and 5 typical carcinoid (TC) samples were included in this study. Tumor sections were immunohistochemically stained for 4F2hc (CD98), glucose transporter 1 (Glut1) and 3 (Glut3), hypoxia-inducible factor-1α (HIF-1α), hexokinase I, vascular endothelial growth factor (VEGF), microvessel density (CD34), epidermal growth factor receptor (EGFR), Akt/mammalian target of rapamycin (mTOR) signaling pathway (p-Akt, p-mTOR and p-S6K) and for a cell cycle regulator (p53). 4F2hc was overexpressed in 0% of the pulmonary carcinoids (TCs and ACs), 62.5% of the LCNECs and 50.0% of the SCLCs. A positive 4F2hc expression was significantly associated with age, histology and Glut1 expression. Moreover, a significant correlation was found between 4F2hc expression, and Glut1, HIF-1α, p-Akt, p-mTOR and p-S6K. The expression of 4F2hc was also significantly associated with poor overall survival. The expression of 4F2hc expression tended to increase from low-grade to high-grade pulmonary NE tumors. Our results suggest that 4F2hc may play a significant role in tumor progression, hypoxic conditions and poor outcome in patients with pulmonary NE tumors. IntroductionNeuroendocrine (NE) tumors of the lung arise from Kulchitzky cells, which are normally present in the bronchial mucosa and share the common morphological features of neuroendocrine tumors, including organoid nesting, palisading, rosettes, or a trabecular growth pattern. These tumors are represented by a wide range of pathological entities (1-5). It is now widely recognized that NE tumors of the lung include a spectrum that ranges from low-grade typical carcinoid (TC) and intermediate-grade atypical carcinoid (AC) to high-grade large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinomas (SCLC) (1-4). However, there has been no established clinical marker, which correlates with the response to the treatment and the prognosis in patients with pulmonary NE tumors. 4F2hc (CD98) is a disulphide-linked 125-kDa heterodimeric membrane glycoprotein, which is found on the cell surface of most normal cells. It was first identified on the cell surface of T lymphocytes (5). However, 4F2hc has been shown to be involved in the cellular proliferation, transformation, fusion, and adhesion and also in the L-type amino acid transport (LAT) system, in addition to regulating integrin activation, and therefore, integrin signaling and anchorage-independent growth. 4F2hc is reconstituted and expressed at high levels on the surface of many types of tumor cells. The overexpression of 4F2hc has been shown to result in cellular transformation (6,7). Recent studies have documented that 4F2hc expression is in...

show abstract

Expression of L-type amino acid transporter 1 (LAT1) in neuroendocrine tumors of the lung

Cited by 57 publications

References 26 publications

miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

In Vivo Biodistribution of No-Carrier-Added 6-¹⁸F-Fluoro-3,4-Dihydroxy-l-Phenylalanine (¹⁸F-DOPA), Produced by a New Nucleophilic Substitution Approach, Compared with Carrier-Added ¹⁸F-DOPA, Prepared by Conventional Electrophilic Substitution

Expression of 4F2hc (CD98) in pulmonary neuroendocrine tumors

Contact Info

Product

Resources

About

Expression of L-type amino acid transporter 1 (LAT1) in neuroendocrine tumors of the lung

Cited by 57 publications

References 26 publications

miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

In Vivo Biodistribution of No-Carrier-Added 6-18F-Fluoro-3,4-Dihydroxy-l-Phenylalanine (18F-DOPA), Produced by a New Nucleophilic Substitution Approach, Compared with Carrier-Added 18F-DOPA, Prepared by Conventional Electrophilic Substitution

Expression of 4F2hc (CD98) in pulmonary neuroendocrine tumors

Contact Info

Product

Resources

About

In Vivo Biodistribution of No-Carrier-Added 6-¹⁸F-Fluoro-3,4-Dihydroxy-l-Phenylalanine (¹⁸F-DOPA), Produced by a New Nucleophilic Substitution Approach, Compared with Carrier-Added ¹⁸F-DOPA, Prepared by Conventional Electrophilic Substitution