Alterations in genes encoding sarcoplasmic-endoplasmic reticulum Ca2+ pumps in association with head and neck squamous cell carcinoma

Korošec, Branka; Glavač, Damjan; Volavšek, Metka; Ravnik‐Glavač, Metka

doi:10.1016/j.cancergencyto.2007.12.003

Cited by 21 publications

(18 citation statements)

References 28 publications

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“…Loss or reduced expression of SERCA2 was also detected in all patients with alterations in the promoter region of the gene, as well as in patients with combinations of gene alterations (159). Similarly, eight different mutations have been found in the ATP2A2 and ATP2A3 genes in 11 patients with head and neck squamous cell carcinoma (160), suggesting that germline alterations of these genes may predispose to cancer and that impaired SERCA genes might be involved, directly or indirectly, as an early event in carcinogenesis.…”

Section: Other Diseases Related To Alterations Of the Serca Pumpsmentioning

confidence: 88%

Calcium Pumps in Health and Disease

Brini¹,

Carafoli²

2009

Physiological Reviews

573

469

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Ca2+-ATPases (pumps) are key actors in the regulation of Ca2+ in eukaryotic cells and are thus essential to the correct functioning of the cell machinery. They have high affinity for Ca2+ and can efficiently regulate it down to very low concentration levels. Two of the pumps have been known for decades (the SERCA and PMCA pumps); one (the SPCA pump) has only become known recently. Each pump is the product of a multigene family, the number of isoforms being further increased by alternative splicing of the primary transcripts. The three pumps share the basic features of the catalytic mechanism but differ in a number of properties related to tissue distribution, regulation, and role in the cellular homeostasis of Ca2+. The molecular understanding of the function of the pumps has received great impetus from the solution of the three-dimensional structure of one of them, the SERCA pump. These spectacular advances in the structure and molecular mechanism of the pumps have been accompanied by the emergence and rapid expansion of the topic of pump malfunction, which has paralleled the rapid expansion of knowledge in the topic of Ca2+-signaling dysfunction. Most of the pump defects described so far are genetic: when they are very severe, they produce gross and global disturbances of Ca2+ homeostasis that are incompatible with cell life. However, pump defects may also be of a type that produce subtler, often tissue-specific disturbances that affect individual components of the Ca2+-controlling and/or processing machinery. They do not bring cells to immediate death but seriously compromise their normal functioning.

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Section: Other Diseases Related To Alterations Of the Serca Pumpsmentioning

confidence: 88%

Calcium Pumps in Health and Disease

Brini¹,

Carafoli²

2009

Physiological Reviews

573

469

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“…Decreased expression of SERCA3 was also noted in transformed gastric cells and lymphocytic cells; however, little or no changes in SERCA2 expression levels were noted in these three cell types in transformed and differentiated states [3]. Furthermore, mutations in SERCA3 have also recently been found to occur in some head and neck squamous cell carcinomas [52]. Cancer cell SERCA isoform expression profiles also appear to be cell-type-specific, since when comparing SERCA2b expression in normal and transformed thyroid cells, a dramatic down-regulation in the expression of this particular isoform was shown to occur [4].…”

Section: Inhibitors As Cancer Therapeutic Agentsmentioning

confidence: 88%

A diversity of SERCA Ca2+ pump inhibitors

Michelangeli

East

2011

Biochemical Society Transactions

131

113

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The SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) is probably the most extensively studied membrane protein transporter. There is a vast array of diverse inhibitors for the Ca2+ pump, and many have proved significant in helping to elucidate both the mechanism of transport and gaining conformational structures. Some SERCA inhibitors such as thapsigargin have been used extensively as pharmacological tools to probe the roles of Ca2+ stores in Ca2+ signalling processes. Furthermore, some inhibitors have been implicated in the cause of diseases associated with endocrine disruption by environmental pollutants, whereas others are being developed as potential anticancer agents. The present review therefore aims to highlight some of the wide range of chemically diverse inhibitors that are known, their mechanisms of action and their binding location on the Ca2+ ATPase. Additionally, some ideas for the future development of more useful isoform-specific inhibitors and anticancer drugs are presented.

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“…17 Recent data suggest that the ATP2A2 gene is also correlated with several cancer types in humans. [19][20][21][22] Although squamous cell carcinoma is not common in patients with DD, 7 cases of oral, subungual, vulval, and scrotal squamous carcinoma have been reported in addition to basal cell carcinoma, melanoma, and non-small cell lung cancer [23][24][25][26][27][28][29] ; in the latter case, sequencing of the ATP2A2 gene revealed 3 polymorphisms and one ATP2A2 mutation (R751Q). 20 No DD patient with cancer has been detected in our cohort; however, the majority of patients were younger than 40 years.…”

Section: Ddmentioning

confidence: 97%