The voltage-dependent K+ channels Kv1.3 and Kv1.5 in human cancer

Abstract

Voltage-dependent K+ channels (Kv) are involved in a number of physiological processes, including immunomodulation, cell volume regulation, apoptosis as well as differentiation. Some Kv channels participate in the proliferation and migration of normal and tumor cells, contributing to metastasis. Altered expression of Kv1.3 and Kv1.5 channels has been found in several types of tumors and cancer cells. In general, while the expression of Kv1.3 apparently exhibits no clear pattern, Kv1.5 is induced in many of the analyzed metastatic tissues. Interestingly, evidence indicates that Kv1.5 channel shows inversed correlation with malignancy in some gliomas and non-Hodgkin's lymphomas. However, Kv1.3 and Kv1.5 are similarly remodeled in some cancers. For instance, expression of Kv1.3 and Kv1.5 correlates with a certain grade of tumorigenicity in muscle sarcomas. Differential remodeling of Kv1.3 and Kv1.5 expression in human cancers may indicate their role in tumor growth and their importance as potential tumor markers. However, despite of this increasing body of information, which considers Kv1.3 and Kv1.5 as emerging tumoral markers, further research must be performed to reach any conclusion. In this review, we summarize what it has been lately documented about Kv1.3 and Kv1.5 channels in human cancer.

Voltage-Gated Ptassium Channels Kv1.3 - Potentially New Molecular Target in Cancer Diagnostics and Therapy

“…First of all, several studies have demonstrated altered expression of Kv1.3 in some cancer specimens in comparison with normal tissue [6-8, 17, 18]. An increased expression of Kv1.3 channels was observed in the case of breast, colon, smooth muscle (leiomyosarcoma), skeletal muscle (alveolar rhabdomyosarcoma) and lymph node cancer [8,17] and in mature neoplastic B cells in chronic lymphocytic leukemia (B-CLL) [20]. A significantly increased expression of Kv1.3 channels that was positively correlated with tumor aggressiveness was recently observed in the case of leiomyosarcoma and alveolar rhabdomyosarcoma [8,18].…”

“…Recently, Kv1.3 channels are considered a new, potentially attractive molecular target in both cancer diagnostics and therapy [6][7][8][17][18][19][20]. First of all, several studies have demonstrated altered expression of Kv1.3 in some cancer specimens in comparison with normal tissue [6-8, 17, 18].…”

“…Kv1.3 channels are expressed abundantly in many tissues, both normal and cancer [6][7][8]. Studies performed in the last 10 years provide evidence that Kv1.3 channels are expressed not only in the plasma membrane, but also in the inner mitochondrial membrane [9,10].…”

Kv1.3: a multifunctional channel with many pathological implications

“…This phenomenon is postulated to be caused by the necessity of a transitory hyperpolarization, which supplies the driving force for Ca 2+ entry during G1/S progression [6]. Additional evidence supports that Kv1.3 would alter cell proliferation independently of ion conduction either by voltage-dependent conformational changes or by phosphorylation of the channel [4].…”

“…In this scenario, inhibition of Kv1.3 would be pointless [4]. On the other hand, Kv1.5 expression exhibits a significant correlation with the degree of malignancy in various kinds of tumors [6]. For all these reasons, future cancer therapies regarding Kv1.3 or Kv1.5 as targets would require exhaustive analysis and caseby-case consideration.…”