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.
Highlights
VOLTAGE-DEPENDENT K+ CHANNELS Kv1.5 are members of the Shaker (Kv1).3 AND Kv1.5 Potassium channels are one of the most diverse and ubiquitous families of membrane proteins and are encoded by more than 75 different genes (Caterall et al, 2002)
We have recently studied the expression pattern of Kv1.3 and Kv1.5 in detail during the early stages of human development, and we have noted the following observations: (1) numerous tissues express Kv1.3 and Kv1.5 channels, (2) both channels are abundantly expressed in fetal liver (Bielanska et al, 2010), which serves as a hematopoietic tissue during early gestation, (3) adult hepatocytes did not express Kv1.3 (Vicente et al, 2003), (4) Kv1.5 is strongly expressed in fetal muscle and heart, whereas Kv1.3 abundance is low, (5) human fetal skeletal muscle expresses slightly more Kv1.3 than adult muscle fibers (Bielanska et al, 2010), and (6) the Kv1.5 channel is predominantly located in adult skeletal muscle and exhibits a cell cycle-dependent regulation pattern (Villalonga et al, 2008)
Several K+ channels are essential for cell proliferation and appear to play a role in the development of cancer
Summary
Many Kv channels, including Kv1.3, Kv1.5, Kv1.6, Kv2.1, and Kv2.2, are present in immortalized gastric epithelial cells and several gastric cancer cells (AGS, KATOIII, MKN28, MKN45, MGC803, SGC7901, SGC7901/ADR, and SGC7901/VCR). IKs currents are related to the development of multi-drug resistance in gastric cancer cells (Wu et al, 2002). Proliferation of several human colon cancer cell lines (SW1116, LoVo, Colo320DM, and LS174t) was increased by two K+ channel activators, minoxidil and diazoxide. Several Kv blockers, including dequalinium and amiodarone, caused a marked growth-inhibition of human colon cancer cell lines. Glibenclamide is another Kv channel blocker that inhibits cellular proliferation (Abdul and Hoosein, 2002a,b). K+ channel inhibitors blocked [Ca2+]i influx, suggesting that K+ channel activity may control the proliferation of colon cancer cells by modulating Ca2+ entry (Yao and Kwan, 1999). Colon biopsies exhibited an increase in Kv1.3 and Kv1.5 expression, this phenomenon may be an artifact of the massive presence of inflammatory cells, which express high levels of both channels (Bielanska et al, 2009)
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