Heterodimeric transporters belong to SLC7 cationic amino acid transporter/glycoprotein-associated family. They are composed of single membrane-spanning glycosylated heavy chains and non-glycosylated multiple membrane-spanning light chains. The light chains are catalytic subunits responsible for substrates transport, whereas the heavy chains are accessory subunits that form complexes with the light chains via a disulfide bond and assist the membrane localization of the heterodimeric complexes. In addition to the roles in membrane sorting of the transporters, one of the heavy chains 4F2hc (4F2 heavy chain; CD98hc; SLC3A2) is involved in multiple protein-protein interactions and generates growth signals presumably through the interactions with integrins. The substrates of such heterodimeric transporters are in general amino acids. Among the heterodimeric transporters, LAT1 (SLC7A5) and xCT (SLC7A11), both of which form heterodimers with 4F2hc, have been demonstrated to be upregulated in cancers. LAT1, as described bellow, mediates uptake of the large neutral amino acids for cellular nutrition and mTOR signaling, whereas xCT is responsible for the uptake of cystine for cellular glutathione production to protect cells from oxidative stress. The upregulation of xCT in cancer stem cells has been reported to be responsible for the resistance to drug and radiation therapy. In terms cellular metabolism, amino acid transporters mediate cellular uptake of amino acids for cells to growth and survive. They are regulated to keep up with the metabolic status so that living cells take up amino acids depending on the metabolic requirements. In tumor cells, amino acid transporters are upregulated to support massive protein synthesis for continuous growth and proliferation. Among amino acid transporters expressed in tumor cells, system L transporters have been proposed to be crucial to supply tumor cells with large neutral amino acids including many essential amino acids. Among them, LAT1 (L-type amino acid transporter 1) is highly expressed in human malignant tumors. In contrast, cells in normal tissues express other amino acid transporters including the other isoform of system L transporter LAT2. We have found that the high expression of LAT1 in tumors is correlated with poor prognosis. Thus, LAT1 can be a molecular target for the diagnosis of cancers. In fact, many radiolabeled amino acid probes used for bio-imaging and diagnosis of cancers are the substrates of LAT1. Among them, 18F-FAMT (L-[3-18F]-alpha-methyltyrosine) is selective for LAT1 and an excellent probe in positron emission tomography (PET ) for the diagnosis of cancers. Different from 18F-FDG (fluorodeoxy glucose) conventionally used for PET diagnosis of cancers, 18F-FAMT is specific to cancers and not accumulated in non-cancerous legions. Additionally, 18F-FAMT can be applied to brain tumors because the brain background is low in 18F-FAMT PET. Because LAT1 is upregulated in tumor cells to support continuous growth and proliferation, the inhibition of LAT1 is expected to suppress cancers. We have examined the effect of inhibition of LAT1 on tumor growth and found that a classical system L inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), and an antisense oligonucleotide designed against LAT1 inhibits the proliferation of tumor cells and suppressed the growth of tumors subcutaneously inoculated to nude mice. In agreement with this, the inhibition of LAT1 by BCH and the antisense oligonucleotide prolongs the survival of tumor-bearing mice. In order to design the LAT1-specific high-affinity inhibitors, we examined the properties of substrate recognition by LAT1. We found that LAT1 relies on the ionic interaction with alpha-carboxyl group and alpha-amino group and on the hydrophobic interaction with the substrates. Based on this, we designed chemical compounds and obtained LAT1 inhibitors with an affinity ~1,000 fold higher that that of BCH. They effectively suppressed tumor growth in vivo and in vitro at lower doses compared with those for BCH. These observations conclude that LAT1 is essential for cancer cell growth and progression of cancers. Additionally, it is proposed that the inhibition of LAT1 could be a new rationale to anti-tumor therapy. In cancer cells, LAT1/4F2hc forms further molecular complexes with other membrane proteins such as integrins, CD147 and amino acid transporter ASCT2. ASCT2 mediates the influx of glutamine and assists the influx of essential amino acids including leucine through LAT1 via exchange mechanism. Such “transportsome” is essential for the activation of mTOR signaling in cancer cells. In the lecture, the role of LAT1/4F2hc heterodimeric complex in cancer cell growth will be discussed in terms cellular signaling originated from both LAT1 and 4F2hc.