LAT1 is a putative therapeutic target in endometrioid endometrial carcinoma

l-type amino acid transporters (LAT1-4) are expressed in various cancer types and are involved in the uptake of essential amino acids such as leucine. Here we investigated the expression of LAT1-4 in endometrial adenocarcinoma and evaluated the contribution of LATs to endometrial cancer cell growth. Analysis of human gene expression data showed that all four LAT family members are expressed in endometrial adenocarcinomas. LAT1 was the most highly expressed, and showed a significant increase in both serous and endometrioid subtypes compared to normal endometrium. Endometrioid patients with the highest LAT1 levels exhibited the lowest disease-free survival. The pan-LAT inhibitor BCH led to a significant decrease in cell growth and spheroid area in four endometrial cancer cell lines tested in vitro. Knockdown of LAT1 by shRNA inhibited cell growth in HEC1A and Ishikawa cells, as well as inhibiting spheroid area in HEC1A cells. These data show that LAT1 plays an important role in regulating the uptake of essential amino acids such as leucine into endometrial cancer cells. Increased ability of BCH compared to LAT1 shRNA at inhibiting Ishikawa spheroid area suggests that other LAT family members may also contribute to cell growth. LAT1 inhibition may offer an effective therapeutic strategy in endometrial cancer patients whose tumours exhibit high LAT1 expression. What's new? The amino acid transporter LAT1 may provide a new avenue for attacking endometrial cancer. Because multiple cancer types express these types of transporters, researchers suspected they might spur endometrial cancer growth. The authors analysed gene expression data and found significantly higher LAT1 expression in cancerous cells than in normal endometrium; furthermore, patients with highest LAT1 expression had lowest survival rates. By knocking down LAT1 expression, the authors showed that the transporter protein mediates leucine uptake and cell growth. Thus, targeting LAT1 could help stop endometrial cancer growth.