Ether à go-go potassium channels and cancer

Camacho, Javier

doi:10.1016/j.canlet.2005.02.016

Cited by 89 publications

(74 citation statements)

References 46 publications

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“…[5][6][7] The contribution of potassium channels to the neoplastic phenotype involves, between others, the control of cell proliferation and apoptosis, or the regulation of invasiveness and metastatic spread. [9][10][11][12][13]22 Owing to their oncogenic properties and location at the cell membrane, members of the EAG channels family have been postulated as promising therapeutic targets for cancer treatment. 11,15 This study is the first to investigate the expression pattern of the HERG1 potassium channel subunit in laryngeal premalignant lesions and invasive carcinomas to ascertain the role of HERG1 in both malignant transformation and tumor progression and its clinical significance in head and neck squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12][13]22 Owing to their oncogenic properties and location at the cell membrane, members of the EAG channels family have been postulated as promising therapeutic targets for cancer treatment. 11,15 This study is the first to investigate the expression pattern of the HERG1 potassium channel subunit in laryngeal premalignant lesions and invasive carcinomas to ascertain the role of HERG1 in both malignant transformation and tumor progression and its clinical significance in head and neck squamous cell carcinoma. Our findings demonstrate that HERG1 is frequently aberrantly expressed in an extraordinarily high percentage of primary tumors (87%) and head and neck squamous cell carcinoma-derived cell lines (100%), whereas no expression was detected in the corresponding normal epithelia, rendering HERG1 expression a reliable tumor marker.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10] Because of their oncogenic properties, distribution, modulation and pharmacology, members of the ether à-go-go (EAG) potassium channels family have gained interest as research tools for detection and therapy of different cancers. [11][12][13][14][15] The EAG potassium channel family comprises three distinct subfamilies: EAG (Kv10), ERG (EAG-related gene; Kv11) and ELK (EAG-like; Kv12). Attempts to clone the human EAG channel led to the detection of the human ERG (HERG) channel.…”

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Role of HERG1 potassium channel in both malignant transformation and disease progression in head and neck carcinomas

et al. 2012

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Evidence indicates that human ether à -go-go-related gene 1 (HERG1) voltage-gated potassium channels could represent new valuable membrane therapeutic targets and diagnostic/prognostic biomarkers in various cancers. This study is the first to investigate the expression pattern of HERG1 potassium channel subunit in both primary tumors and precancerous lesions to establish its clinical and biological role during the development and progression of head and neck squamous cell carcinomas. HERG1 protein expression was evaluated by immunohistochemistry in paraffin-embedded tissue specimens from 133 patients with laryngeal/ hypopharyngeal squamous cell carcinomas and 75 patients with laryngeal dysplasia, and correlated with clinical data. Our findings demonstrate that HERG1 is frequently aberrantly expressed in a high percentage of primary tumors (87%), whereas expression was negligible in both stromal cells and normal-adjacent epithelia. HERG1 expression increased during head and neck squamous cell carcinoma progression and was significantly associated with lymph node metastasis (P ¼ 0.04), advanced disease stages (Po0.001), regional tumor recurrence (P ¼ 0.004), distant metastasis (P ¼ 0.03) and reduced disease-specific survival (P ¼ 0.012, logrank test). HERG1-positive expression was also detected in 31 (41%) of 75 laryngeal dysplasias. Interestingly, HERG1 expression increased with the grade of dysplasia; however, HERG1 expression but not histology correlated significantly with increased laryngeal cancer risk (P ¼ 0.007). In addition, functional studies in head and neck squamous cell carcinoma-derived cell lines further revealed that HERG1 expression promotes anchorage-dependent and -independent cell growth and invasive capability, although independently of its ionconducting function. Our data demonstrate that HERG1 expression is a biologically and clinically relevant feature in head and neck squamous cell carcinoma progression and also during malignant transformation, and a promising candidate as cancer risk marker and therapeutic target for head and neck squamous cell carcinoma prevention and treatment. Keywords: cancer risk; dysplasia; head and neck squamous cell carcinoma; HERG1; immunohistochemistry; metastasis; potassium channelThe incidence of head and neck squamous cell carcinoma has been gradually increasing over the last three decades. It is the sixth leading cancer by incidence worldwide and only 40-50% of patients with head and neck squamous cell carcinoma will survive for 5 years.1 Two-thirds of the diagnosed tumors present with locally advanced or metastatic disease (stages III and IV) and patients survival is determined by the development of loco-regional recurrences, distant metastases and second primary tumors.2 In this context, the Received

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Role of HERG1 potassium channel in both malignant transformation and disease progression in head and neck carcinomas

et al. 2012

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“…On the other hand, inhibition of either channel activity or expression decreases proliferation of tumor cells both in vitro and in vivo (Pardo et al, 1999;Ousingsawat et al, 2007;Gómez-Varela et al 2007;Downie et al, 2008;Díaz et al, 2009). Therefore, Eag is also a promising therapeutic target for many types of cancer (Camacho, 2006;.…”

Section: Oncogenic Eag1 K + Channels In Cervical Cancer and Regulatiomentioning

confidence: 99%

The Human Papilloma Virus – Ion Channel Link in Cancer: An Alternative Opportunity for Diagnosis and Therapy

Ramírez¹,

Camacho²

2012

Human Papillomavirus and Related Diseases - From Bench to Bedside - Research Aspects

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“…[1] Most of these activities are directly or indirectly proposed to promote the complex process of cancer formation by various mechanisms. [2] Among different types of ion channels, abnormal expression of voltage gated K + channels (I K ) is reported in many cancer cells including prostate, [3] breast, [4] colon, [5] and glial.…”

Section: Introductionmentioning

confidence: 99%

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Malathi

2017

AJP

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Background: Phenolic compounds are ubiquitous in dietary fruits and vegetables and have been proposed to have antioxidant, antibacterial, anti-inflammatory, and anticancer effects. Voltage gated K + channels (I K ) contribute to various cellular mechanisms involved in the tumor cell progression. Therefore, the modulation of I K current may be a potential target for cancer therapy. In this study, we electrophysiologically characterized four phenolic compounds for their modulatory activities on I K currents. Materials and Methods: The whole cell configuration of the patch clamp recording technique was used to record the I K currents from human prostate cancer line (LNCaP). In addition, 200 µM of phenolic compounds (curcumin, resveratrol, rutin, and troxerutin) were externally perfused to the cells. Results: Obtained results provide evidence that resveratrol at 200 µM inhibited more than half of the I K current amplitude. On the other hand, curcumin, rutin, and troxerutin did not show any modulatory effect on I K current in LNCaP cells. Conclusion: This study demonstrates that not all the anticancer compounds are effective inhibitors of I K current, but only few of them. The I K current inhibitors might exhibit effective antimetastatic properties.

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Ether à go-go potassium channels and cancer

Cited by 89 publications

References 46 publications

Role of HERG1 potassium channel in both malignant transformation and disease progression in head and neck carcinomas

Role of HERG1 potassium channel in both malignant transformation and disease progression in head and neck carcinomas

The Human Papilloma Virus – Ion Channel Link in Cancer: An Alternative Opportunity for Diagnosis and Therapy

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