Amino acid transporters ASCT2 and LAT1 in cancer: Partners in crime?

Fuchs, Bryan C.; Bode, Barrie P.

doi:10.1016/j.semcancer.2005.04.005

Cited by 595 publications

(583 citation statements)

References 102 publications

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“…A second protein is ASCT2. LAT1 transports neutral amino acid with long side chains, such as leucine, and simultaneously counter transports intracellular glutamine [38,39]. The intracellular glutamine supply is maintained via the intracellular Na + -dependent amino acid transporter ASCT2 that helps facilitate LAT1 function.…”

Section: Discussionmentioning

confidence: 99%

Relationship between [ 14 C]MeAIB uptake and amino acid transporter family gene expression levels or proliferative activity in a pilot study in human carcinoma cells: Comparison with [ 3 H]methionine uptake

Kagawa

Nishii

Higashi³

et al. 2017

Nuclear Medicine and Biology

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Results and Conclusion: [ 14 C]MeAIB uptake occurred principally via a Na + -dependent A type mechanism whereas [ 3 H]MET uptake, which occurred predominantly via a Na + -independent L type mechanism although other transporters were also utilized depending on cell type. There was no correlation between [ 3 H]MET uptake and total system L amino acid transporter (LAT) expression. In contrast, [ 14 C]MeAIB uptake strongly correlated with total system A amino acid transporter (SNAT) expression and proliferative activity in this preliminary study using four human carcinoma cell lines. Carcinoma proliferative activity also correlated with total SNAT expression.

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Section: Discussionmentioning

confidence: 99%

Relationship between [ 14 C]MeAIB uptake and amino acid transporter family gene expression levels or proliferative activity in a pilot study in human carcinoma cells: Comparison with [ 3 H]methionine uptake

Kagawa

Nishii

Higashi³

et al. 2017

Nuclear Medicine and Biology

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“…LAT1 is widely expressed in primary human cancers and several cancer cell lines, where it has been shown to play essential roles in growth and survival (Fuchs and Bode, 2006). While it is currently unclear why LAT1 is coveted by transformed cell, Fuchs et al hypothesize that LAT1 provides the essential amino acids that act as signal to enhance growth of cancer cells via mammalian target-of-rapamycin (mTOR)-stimulated translation (Fuchs and Bode, 2006). Likewise, mTOR regulates amino acid transporter gene expression and trafficking to the plasma membrane in response to the growth signal (Fuchs and Bode, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…While it is currently unclear why LAT1 is coveted by transformed cell, Fuchs et al hypothesize that LAT1 provides the essential amino acids that act as signal to enhance growth of cancer cells via mammalian target-of-rapamycin (mTOR)-stimulated translation (Fuchs and Bode, 2006). Likewise, mTOR regulates amino acid transporter gene expression and trafficking to the plasma membrane in response to the growth signal (Fuchs and Bode, 2006). Moreover, overexpression of LAT1 was described to be associated with metastasis in vivo (Ohkame et al, 2001;Tamai et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…When colon cancer RCN-9 cells were injected into the spleen of rats, the size of the resultant metastatic liver tumours was directly correlated to LAT1 expression (Ohkame et al, 2001;Tamai et al, 2001). Thus, inhibition of LAT1 function could be a potential therapeutic strategy for many types of cancer Fuchs and Bode, 2006). Whereas, LAT1 has been shown to mediate the uptake of a number of amino acidrelated compounds such as L-dopa, triiodothyronine, thyroxin, and the anti-cancer agent melphalan (L-phenylalanine mustard, L-PAM, Alkeran, L-Sarcolysin) (Uchino et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I–III nonsmall cell lung cancer

et al. 2008

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The clinical significance of L-type amino acid transporter 1 (LAT1) expression remains unclear, whereas many experimental studies have demonstrated that LAT1 is associated with the proliferation of cancer cells. The purpose of this study was to evaluate the prognostic value of LAT1 in patients with nonsmall cell lung cancer (NSCLC). A total of 321 consecutive patients with completely resected pathologic stage I -III NSCLC were retrospectively reviewed. Expression of LAT1 and proliferative activity, as determined by the Ki-67 labelling index, was also evaluated immunohistochemically and correlated with the prognosis of patients who underwent complete resection of the tumour. Expression of LAT1 was positive in 163 patients (51%) (29% of adenocaricnoma (58 of 200 patients), 91% of squamous cell carcinoma (91 of 100 patients), and 67% of large cell carcinoma (14 of 21 patients)). The 5-year survival rate of LAT1-positive patients (51.8%) was significantly worse than that of LAT1-negative patients (87.8%; Po0.001). L-type amino acid transporter 1 expression was significantly associated with lymph node metastasis and disease stage. Multivariate analysis confirmed that positive expression of LAT1 was an independent factor for predicting a poor prognosis. There was a significant correlation between LAT1 expression and Ki-67 labelling index. LAT1 expression is a promising pathological factor to predict the prognosis in patients with resectable stage I -III NSCLC.

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“…LAT1, the light subunit of system L, is overexpressed in certain primary human tumors. It transports essential neutral amino acids with long, branched, or aromatic side chains required by tumor cells to support their unabated growth (12). Therefore, amino acid transporters like LAT1 are attractive anticancer drug targets.…”

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confidence: 99%

Substrate Binding Tunes Conformational Flexibility and Kinetic Stability of an Amino Acid Antiporter

Bippes

Zeltina

Casagrande

et al. 2009

Journal of Biological Chemistry

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We used single molecule dynamic force spectroscopy to unfold individual serine/threonine antiporters SteT from Bacillus subtilis. The unfolding force patterns revealed interactions and energy barriers that stabilized structural segments of SteT. Substrate binding did not establish strong localized interactions but appeared to be facilitated by the formation of weak interactions with several structural segments. Upon substrate binding, all energy barriers of the antiporter changed thereby describing the transition from brittle mechanical properties of SteT in the unbound state to structurally flexible conformations in the substrate-bound state. The lifetime of the unbound state was much shorter than that of the substrate-bound state. This leads to the conclusion that the unbound state of SteT shows a reduced conformational flexibility to facilitate specific substrate binding and a reduced kinetic stability to enable rapid switching to the bound state. In contrast, the bound state of SteT showed an increased conformational flexibility and kinetic stability such as required to enable transport of substrate across the cell membrane. This result supports the working model of antiporters in which alternate substrate access from one to the other membrane surface occurs in the substrate-bound state.

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Amino acid transporters ASCT2 and LAT1 in cancer: Partners in crime?

Cited by 595 publications

References 102 publications

Relationship between [ 14 C]MeAIB uptake and amino acid transporter family gene expression levels or proliferative activity in a pilot study in human carcinoma cells: Comparison with [ 3 H]methionine uptake

Relationship between [ 14 C]MeAIB uptake and amino acid transporter family gene expression levels or proliferative activity in a pilot study in human carcinoma cells: Comparison with [ 3 H]methionine uptake

Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I–III nonsmall cell lung cancer

Substrate Binding Tunes Conformational Flexibility and Kinetic Stability of an Amino Acid Antiporter

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