Fliegel Larry
Department of Biochemistry, University of Alberta, Edmonton, AB, Canada.
Rev Physiol Biochem Pharmacol. 2022;182:85-110. doi: 10.1007/112_2020_18.
Prostate cancer is the fourth most commonly diagnosed cancer, and although it is often a slow-growing malignancy, it is the second leading cause of cancer-associated deaths in men and the first in Europe and North America. In many forms of cancer, when the disease is a solid tumor confined to one organ, it is often readily treated. However, when the cancer becomes an invasive metastatic carcinoma, it is more often fatal. It is therefore of great interest to identify mechanisms that contribute to the invasion of cells to identify possible targets for therapy. During prostate cancer progression, the epithelial cells undergo epithelial-mesenchymal transition that is characterized by morphological changes, a loss of cell-cell adhesion, and invasiveness. Dysregulation of pH has emerged as a hallmark of cancer with a reversed pH gradient and with a constitutively increased intracellular pH that is elevated above the extracellular pH. This phenomenon has been referred to as "a perfect storm" for cancer progression. Acid-extruding ion transporters include the Na/H exchanger NHE1 (SLC9A1), the NaHCO cotransporter NBCn1 (SLC4A7), anion exchangers, vacuolar-type adenosine triphosphatases, and the lactate-H cotransporters of the monocarboxylate family (MCT1 and MCT4 (SLC16A1 and 3)). Additionally, carbonic anhydrases contribute to acid transport. Of these, several have been shown to be upregulated in different human cancers including the NBCn1, MCTs, and NHE1. Here the role and contribution of acid-extruding transporters in prostate cancer growth and metastasis were examined. These proteins make significant contributions to prostate cancer progression.
前列腺癌是第四大最常被诊断出的癌症，尽管它通常是一种生长缓慢的恶性肿瘤，但它是男性癌症相关死亡的第二大主要原因，在欧洲和北美则位居榜首。在许多癌症类型中，当疾病是局限于一个器官的实体瘤时，通常很容易治疗。然而，当癌症发展成为侵袭性转移性癌时，往往会致命。因此，确定促成细胞侵袭的机制以识别可能的治疗靶点具有重大意义。在前列腺癌进展过程中，上皮细胞会经历上皮-间质转化，其特征是形态变化、细胞间黏附丧失和侵袭性。pH失调已成为癌症的一个标志，表现为pH梯度反转以及细胞内pH持续升高，高于细胞外pH。这种现象被称为癌症进展的“完美风暴”。酸外排离子转运体包括钠/氢交换体NHE1（SLC9A1）、钠/碳酸氢根共转运体NBCn1（SLC4A7）、阴离子交换体、液泡型腺苷三磷酸酶以及单羧酸家族的乳酸-氢共转运体（MCT1和MCT4（SLC16A1和3））。此外，碳酸酐酶也参与酸的转运。其中，有几种已被证明在包括NBCn1、MCTs和NHE1在内的不同人类癌症中上调。在此研究了酸外排转运体在前列腺癌生长和转移中的作用及贡献。这些蛋白质对前列腺癌的进展有重大贡献。
