One of the major obstacles to the successful treatment of cancer is the complex biology of solid tumour development. Although regulation of intracellular pH has been shown to be critically important for many cellular functions, pH regulation has not been fully investigated in the field of cancer. It has, however, been shown that cellular pH is crucial for biological functions such as cell proliferation, invasion and metastasis, drug resistance and apoptosis. Hypoxic conditions are often observed during the development of solid tumours and lead to intracellular and extracellular acidosis. Cellular acidosis has been shown to be a trigger in the early phase of apoptosis and leads to activation of endonucleases inducing DNA fragmentation. To avoid intracellular acidification under such conditions, pH regulators are thought to be up-regulated in tumour cells. Four major types of pH regulator have been identified: the proton pump, the sodium-proton exchanger family (NHE), the bicarbonate transporter family (BCT) and the monocarboxylate transporter family (MCT). Here, we describe the structure and function of pH regulators expressed in tumour tissue. Understanding pH regulation in tumour cells may provide new ways of inducing tumour-specific apoptosis, thus aiding cancer chemotherapy.

中文翻译：

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细胞pH调节剂：癌症化学疗法的潜在有希望的分子靶标。

成功治疗癌症的主要障碍之一是实体瘤发展的复杂生物学。尽管已经显示细胞内pH的调节对于许多细胞功能至关重要，但是在癌症领域尚未对pH调节进行全面研究。然而，已经表明细胞pH对于生物学功能如细胞增殖，侵袭和转移，耐药性和细胞凋亡至关重要。在实体瘤的发展过程中经常观察到缺氧状况，并导致细胞内和细胞外酸中毒。细胞酸中毒已被证明是凋亡早期的触发因素，并导致内切核酸酶活化，从而诱导DNA片段化。为了避免在这种条件下发生细胞内酸化，人们认为pH调节剂在肿瘤细胞中被上调。已确定了四种主要的pH调节剂类型：质子泵，钠-质子交换剂家族（NHE），碳酸氢盐转运蛋白家族（BCT）和单羧酸盐转运蛋白家族（MCT）。在这里，我们描述了在肿瘤组织中表达的pH调节剂的结构和功能。了解肿瘤细胞的pH调节可能提供诱导肿瘤特异性凋亡的新方法，从而有助于癌症化疗。