Breast cancer (BC) is the most common cancer among women worldwide. Due to its complexity in nature, effective BC treatment can encounter many challenges. The human RALBP1 gene encodes a 76-kDa splice variant protein, RLIP (ral-binding protein1, RalBP1), a stress-protective mercapturic acid pathway (MAP) transporter protein, that also plays a key role in regulating clathrin-dependent endocytosis (CDE) as a Ral effector. Growing evidence shows that targeting RLIP may be an effective strategy in cancer therapy, as RLIP is over-expressed in multiple cancers and is known to induce resistance to apoptosis and chemotherapeutic drugs. Recent studies demonstrated that RLIP is expressed in human BC tissues, as well as BC cell lines. Knockdown of RLIP resulted in apoptotic death of BC cells in vitro, and targeted inhibition and depletion of RLIP resulted in regression of BC in xenograft studies of nude mice. Signaling studies showed that RLIP depletion inhibited endocytosis and differentially regulated signaling to Akt, Myc, and ERK1/2. However, the proliferation and multi-specific transport mechanisms that promote RLIP-mediated cell death in BC are not well understood. In this review, we will discuss a missing but an essentially determining and connecting piece of the puzzle on the understanding of proliferation and transport mechanisms by focused analyses of the apoptotic, drug- and radiation-sensitivity regulated by RLIP, a stress-responsive non-ATP-binding cassette (ABC), high capacity MAP transporter, in breast cancer.

乳腺癌 (BC) 是全世界女性中最常见的癌症。由于其性质的复杂性，有效的 BC 治疗可能会遇到许多挑战。人类RALBP1基因编码 76-kDa 剪接变异蛋白 RLIP（ral 结合蛋白 1，RalBP1），一种应激保护性硫醇尿酸途径 (MAP) 转运蛋白，在调节网格蛋白依赖性内吞作用 (CDE) 中也起着关键作用) 作为 Ral 效应器。越来越多的证据表明，靶向 RLIP 可能是一种有效的癌症治疗策略，因为 RLIP 在多种癌症中过度表达，并且已知会诱导对细胞凋亡和化疗药物的耐药性。最近的研究表明，RLIP 在人类 BC 组织以及 BC 细胞系中表达。RLIP 的敲低导致 BC 细胞的凋亡性死亡在体外，RLIP 的靶向抑制和消耗导致裸鼠异种移植研究中 BC 的消退。信号转导研究表明，RLIP 耗竭抑制内吞作用并差异调节 Akt、Myc 和 ERK1/2 的信号转导。然而，促进 BC 中 RLIP 介导的细胞死亡的增殖和多特异性转运机制尚不清楚。在这篇综述中，我们将通过对 RLIP 调节的细胞凋亡、药物和辐射敏感性的重点分析，讨论一个缺失但本质上决定和连接的拼图，了解增殖和运输机制，RLIP 是一种应激反应非ATP 结合盒 (ABC)，高容量 MAP 转运体，在乳腺癌中。