SLC35F2 in Cancer Development and Progression.

Abstract

Solute carrier family 35 member F2 (SLC35F2) is a transporter located predominantly at the plasma membrane and Golgi apparatus and is predicted to contain ten transmembrane helices. Recent studies have identified SLC35F2 as the only currently known queuosine (Q)-specific transporter in human cells and as the principal high-affinity transporter of queuine (q), although it is not the absolutely exclusive route for q uptake. SLC35F2 is also aberrantly expressed in multiple cancers and has been associated with cell proliferation, migration, invasion, chemoresistance, and ferroptosis regulation. However, the available evidence derives mainly from database analyses, individual cell-based studies, and limited animal experiments and does not yet demonstrate that its tumor-promoting effects directly depend on q/Q uptake or tRNA queuosine modification. SLC35F2 is also an important uptake transporter for the anticancer agent YM155, and its expression can influence intracellular drug exposure and DNA-damage toxicity. YM155 was initially classified as a survivin transcriptional inhibitor, but subsequent studies indicate that its actions also involve DNA intercalation and oxidative DNA damage. Previous clinical trials did not prospectively stratify patients by SLC35F2 expression and showed limited overall efficacy; consequently, its clinical value remains translationally uncertain and biomarker-dependent. Using a structured narrative-review approach, this article critically evaluates the structure and localization of SLC35F2, q/Q transport, regulation of its expression and protein stability, tumor-associated functions, and YM155 delivery. It distinguishes replicated mechanisms from findings supported by single studies and from testable hypotheses, thereby providing a framework for future mechanistic research and precision drug delivery.