Transcriptional regulation of the LAT-1/CD98 light chain

Padbury, Jamés F.; Diah, Sri K.; McGonnigal, Bethany; Miller, Carla K.; Fugère, Céline; Kuzniar, Magdalena; Thompson, Nancy L.

doi:10.1016/j.bbrc.2004.04.062

Cited by 10 publications

(14 citation statements)

References 29 publications

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“…This interpretation is further supported by our findings showing that stable expression of CD147 in HEK293 cells did not increase the level of MCT1. Similar results have been reported for regulation of expression of the heteromeric neutral amino acid transporter CD98/LAT (34). Taken together, these results show that overexpression of the transporter, but not the accessory protein, can increase expression of the functional MCT/ CD147 transporter complex.…”

Section: Discussionsupporting

confidence: 88%

Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231

Gallagher¹,

Castorino

Wang³

et al. 2007

Cancer Research

255

237

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Metastatic cancer cells increase glucose consumption and metabolism via glycolysis, producing large quantities of lactate. Recent work has shown that lactate efflux is mediated by monocarboxylate transporters (MCT), which are composed of a catalytic unit (MCT) and an accessory subunit (CD147), comprising the functional lactate transporter. CD147, an extracellular matrix metalloproteinase (MMP) inducer, is highly expressed in metastatic cancer cells. Because aerobic glycolysis is a hallmark of metastatic cancer, we examined whether increases in CD147 expression were linked to MCT expression in MDA-MB-231, a highly metastatic breast cancer cell line. MCT4 mRNA and protein expression were increased in MDA-MB-231 cells compared with cells derived from normal mammary tissue. MCT4 colocalized with CD147 in the plasma membrane and in membrane blebs shed from the cell surface. Small interfering RNA-mediated silencing of MCT4 impaired the maturation and trafficking of CD147 to the cell surface, resulting in accumulation of CD147 in the endoplasmic reticulum. Silencing MCT4 also resulted in fewer membrane blebs and decreased migration of MDA-MB-231 cells in vitro. Knockdown of CD147 resulted in loss of MCT4 in the plasma membrane and accumulation of the transporter in endolysosomes. These studies establish for the first time that increased expression of CD147 in metastatic cancer cells is coupled to the up-regulation of MCT4. The synergistic activities of the MCT/CD147 complex could facilitate migration of tumor cells by CD147-mediated MMP induction and lactate-stimulated angiogenesis and hyaluronan production. These data provide a molecular link between two hallmarks of metastatic cancer: the glycolytic switch and increased expression of CD147. [Cancer Res 2007;67(9):4182-9]

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Section: Discussionsupporting

confidence: 88%

Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231

Gallagher¹,

Castorino

Wang³

et al. 2007

Cancer Research

255

237

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“…Three members from the SLC7 family, the system y+ encoding gene Slc7a1 (CAT-1) [39], the system L encoding gene Slc7a5 (LAT-1) [40], and Slc7a11 (xCT) from system xc- [41], had induced gene expression in the hypothalamic cell line, and all three were among the top five most upregulated amino acid transporters at 5 h of deprivation. Slc7a1 [28,42], Slc7a5 [23], and Slc7a11 [24] all have been found to respond with increased gene expression following amino acid starvation in several studies. Slc7a11 forms a dimer with the heavy subunit Slc3a2, a cysteine/glutamate exchanger, belonging to system xc- [43].…”

Section: Discussionmentioning

confidence: 99%

The gene expression of numerous SLC transporters is altered in the immortalized hypothalamic cell line N25/2 following amino acid starvation

et al. 2017

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Amino acids are known to play a key role in gene expression regulation, and in mammalian cells, amino acid signaling is mainly mediated via two pathways, the mammalian target of rapamycin complex 1 (mTORC1) pathway and the amino acid responsive (AAR) pathway. It is vital for cells to have a system to sense amino acid levels, in order to control protein and amino acid synthesis and catabolism. Amino acid transporters are crucial in these pathways, due to both their sensing and transport functions. In this large‐scale study, an immortalized mouse hypothalamic cell line (N25/2) was used to study the gene expression changes following 1, 2, 3, 5 or 16 h of amino acid starvation. We focused on genes encoding solute carriers (SLCs) and putative SLCs, more specifically on amino acid transporters. The microarray contained 28 270 genes and 86.2% of the genes were expressed in the cell line. At 5 h of starvation, 1001 genes were upregulated and 848 genes were downregulated, and among these, 47 genes from the SLC superfamily or atypical SLCs were found. Of these, 15 were genes encoding amino acid transporters and 32 were genes encoding other SLCs or atypical SLCs. Increased expression was detected for genes encoding amino acid transporters from system A, ASC, L, N, T, xc‐, and y+. Using GO annotations, genes involved in amino acid transport and amino acid transmembrane transporter activity were found to be most upregulated at 3 h and 5 h of starvation.

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“…It has previously been reported that several genes encoding characterized amino acid transporters from the SLC superfamily, are upregulated following amino acid deprivation in cells, e.g. Slc38a2 (Palii et al 2006 ), Slc7a1 (Fernandez et al 2003 ), Slc7a5 (Padbury et al 2004 ), Slc7a11 (Sato et al 2004 ), Slc1a4 and Slc3a2 (Lee et al 2008 ). However, not all amino acid transporters are regulated in response to amino acid starvation and the increased expression levels detected for Mfsd1 do not necessarily mean that it is an amino acid transporter.…”

Section: Discussionmentioning

confidence: 99%

The Novel Membrane-Bound Proteins MFSD1 and MFSD3 are Putative SLC Transporters Affected by Altered Nutrient Intake

et al. 2016

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Membrane-bound solute carriers (SLCs) are essential as they maintain several physiological functions, such as nutrient uptake, ion transport and waste removal. The SLC family comprise about 400 transporters, and we have identified two new putative family members, major facilitator superfamily domain containing 1 (MFSD1) and 3 (MFSD3). They cluster phylogenetically with SLCs of MFS type, and both proteins are conserved in chordates, while MFSD1 is also found in fruit fly. Based on homology modelling, we predict 12 transmembrane regions, a common feature for MFS transporters. The genes are expressed in abundance in mice, with specific protein staining along the plasma membrane in neurons. Depriving mouse embryonic primary cortex cells of amino acids resulted in upregulation of Mfsd1, whereas Mfsd3 is unaltered. Furthermore, in vivo, Mfsd1 and Mfsd3 are downregulated in anterior brain sections in mice subjected to starvation, while upregulated specifically in brainstem. Mfsd3 is also attenuated in cerebellum after starvation. In mice raised on high-fat diet, Mfsd1 was specifically downregulated in brainstem and hypothalamus, while Mfsd3 was reduced consistently throughout the brain.

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Transcriptional regulation of the LAT-1/CD98 light chain

Cited by 10 publications

References 29 publications

Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231

Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231

The gene expression of numerous SLC transporters is altered in the immortalized hypothalamic cell line N25/2 following amino acid starvation

The Novel Membrane-Bound Proteins MFSD1 and MFSD3 are Putative SLC Transporters Affected by Altered Nutrient Intake

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