The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

Abstract

Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity and patient outcome. This study aimed to evaluate the biological and prognostic value of the membrane solute carrier, SLC3A2 in BC with emphasis on the intrinsic molecular subtypes. SLC3A2 was assessed at the genomic level, using METABRIC data (n = 1980), and at the proteomic level, using immunohistochemistry on tissue microarray (TMA) sections constructed from a large well-characterised primary BC cohort (n = 2500). SLC3A2 expression was correlated with clinicopathological parameters, molecular subtypes and patient outcome. SLC3A2 mRNA and protein expression were strongly correlated with higher tumour grade and poor Nottingham prognostic index (NPI). High expression of SLC3A2 was observed in triple-negative (TN), HER2+ and ER+ high-proliferation subtypes. SLC3A2 mRNA and protein expression were significantly associated with the expression of c-MYC in all BC subtypes (p < 0.001). High expression of SLC3A2 protein was associated with poor patient outcome (p < 0.001), but only in the ER+ high-proliferation (p = 0.01) and TN (p = 0.04) subtypes. In multivariate analysis SLC3A2 protein was an independent risk factor for shorter BC-specific survival (p < 0.001). SLC3A2 appears to play a role in the aggressive BC subtypes driven by MYC and could act as a potential prognostic marker. Functional assessment is necessary to reveal its potential therapeutic value in the different BC subtypes.

The combined expression of solute carriers is associated with a poor prognosis in highly proliferative ER+ breast cancer

“…SLC7A5 requires a covalent association with the heavy chain of the membrane protein, solute carrier family 3 member 2 (SLC3A2), for its functional expression in plasma membrane [13]. We have previously described the potential utility of these two solute carriers as prognostic factors for the highly proliferative BC subtypes [14,15]. Additionally, other studies have revealed the prognostic value of the co-operative expression of SLC7A5 and SLC3A2 in transitional cell carcinoma [16], squamous cell carcinoma of the lung [17] and pulmonary adenocarcinoma [18].…”

Hypoxia-induced switch in SNAT2/SLC38A2 regulation generates endocrine-resistance in breast cancer

“…This is particularly interesting as the luminal B subtype (ER+ subtype) has aggressive clinical behavior, with prognosis similar to that of HER2-enriched and basal-like group and a lower sensitivity to endocrine treatment compared to luminal A ER+ breast cancer (59). Interestingly, recent studies showed that a high expression of different AA transporters, such as SLC3A2 or SLC7A5, is related to poor outcomes in luminal B ER+ breast cancer subtype (60, 61). These data suggest that this subtype might be particular vulnerable to glutamine depletion.…”

Structural differences between the ectodomains of murine and human CD98hc

“…In line with these biological functions, overexpression of CD98hc has been observed in various solid and hematological malignancies, such as non‐small cell lung cancer (NSCLC), breast cancer, colorectal cancer and acute myeloid leukemia (AML) . In general, the overexpression of CD98 is associated with poor prognosis for cancer patients, thus rendering it a promising tumor target for diagnosis and therapy.…”