SLC2A5 promotes lung adenocarcinoma cell growth and metastasis by enhancing fructose utilization

Abstract

The metabolism of cancer cells is highly plastic. Cancer cells can change their preference for nutrient uptake under nutrient stress. Fructose is one of the most common carbohydrates in diet and its metabolism is also involved in the development and progression of tumors. GLUT5, encoded by SLC2A5, is the specific fructose transporter in mammalian cells. In this study, we found that SLC2A5 is significantly upregulated in lung adenocarcinoma (LUAD) patients and overexpression of SLC2A5 is highly correlated with poor prognosis of LUAD patients. The expression of SLC2A5 determined fructose uptake and utilization efficacy in LUAD cells. GLUT5 is critical for the survival of LUAD cells in fructose-containing culture medium. Depletion of SLC2A5 undermined cell proliferation and invasion meanwhile increased cell apoptosis. Overexpression of SLC2A5 enhances cell proliferation, migration, invasion, and tumorigenic. Compared to glucose, fructose is prone to strengthen intracellular-free fatty acid accumulation and ATP production. Moreover, inhibition of GLUT5 by specific small chemical inhibitor sensitizes LUAD cells to paclitaxel treatment. Taken together, our results suggest that GLUT5 could be a potential target alone or combination with other treatment for lung cancer therapy.

<p>GLUT5 increases fructose utilization in ovarian cancer</p>

“…In addition, it has been found that the glucose transporter GLUT1 is highly expressed in the primary lung cancer, but the fructose transporter GLUT5 is highly expressed in the metastasis, suggesting that fructose plays an important role in the metastasis of lung cancer. 15 From all the results, we found that fructose could be used by ovarian cancer cells, and GLUT5 was necessary for this utilization. GLUT5 was expressed at a significantly higher level in ovarian cancer tissues, and its higher expression was correlated with malignant progression, and poor survival of patients.…”

“…17,25 GLUT5, as a specific fructose transporter in mammalian cells, has also been found highly expressed in breast cancer, glioma, lung cancer and so on, and silencing GLUT5 could significantly inhibit these cancer cells growth in fructose medium. 13,[15][16][17][18]23 In this study, we used a similar method to silence GLUT5 in ovarian cancer cells to explore the role the GLUT5 in fructose metabolism in ovarian cancer. As expected, silencing GLUT5 could significantly inhibit the abilities of proliferation, colony formation, and migration in fructose medium, which suggested that GLUT5 was necessary for fructose utilization in ovarian cancer cells.…”

“…According to published reports, many cancer cells, including breast cancer, glioma, and lung cancer, could utilize fructose to maintain their survival and proliferation. 13,[15][16][17] We first collected many kinds of cancer cell lines (Hela, A549, T47D, LN229, AGS, OVCAR8, and SKOV3), and detected their survival after cultured in medium with added glucose or fructose in 72 hrs. Then we found that, compared to glucose-free medium, fructose could successfully promote all these cell Figure 1A).…”

SLC2A5 overexpression in childhood philadelphia chromosome‐positive acute lymphoblastic leukaemia

“…Previous research showed that SLC2A5 ‐mediated fructose utilisation might play an important role in cancer cell growth and survival (Chen et al , ; Weng et al , ). In our study, the addition of fructose protected SUP‐B15 cells from nutrient deficiency‐induced cell death (Fig A, B).…”

“…SLC2A5 encodes SLC2A5 (previously termed GLUT5), which belongs to the glucose transporter proteins family, and facilitates fructose uptake by cells (Barron et al , ). Previous research showed that SLC2A5 was upregulated in various human cancers, such as breast cancer (Macheda et al , ), renal carcinoma (Medina Villaamil et al , ), lung cancer (Weng et al , ) and leukaemia (Chen et al , ). The leukaemia study showed that SLC2A5 promoted acute myeloid leukaemia (AML) fructose utilisation and chemoresistance (Chen et al , ).…”