Golgi Calcium Pump Secretory Pathway Calcium ATPase 1 (SPCA1) Is a Key Regulator of Insulin-like Growth Factor Receptor (IGF1R) Processing in the Basal-like Breast Cancer Cell Line MDA-MB-231

Grice, Desma M.; Vetter, Irina; Faddy, Helen M.; Kenny, Paraic A.; Roberts‐Thomson, Sarah J.; Monteith, Gregory R.

doi:10.1074/jbc.m110.163329

Cited by 76 publications

(73 citation statements)

References 52 publications

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“…Cytosolic free Ca 2+ ([Ca 2+ ] CYT ) was assessed using a Fluorometric Imaging Plate Reader (FLIPR TETRA , Molecular Devices) and the BD PBX no-wash Ca 2+ Assay Kit (BD Biosciences) as described previously (Grice et al, 2010). Cells were seeded at 1×10 4 cells per well in 96-well black plates (Corning Costar).…”

Section: +mentioning

confidence: 99%

TRPC1 is a differential regulator of hypoxia-mediated events and Akt signalling in PTEN-deficient breast cancer cells

Azimi

Milevskiy

Kaemmerer

et al. 2017

Journal of Cell Science

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Hypoxia is a feature of the tumour microenvironment that promotes invasiveness, resistance to chemotherapeutics and cell survival. Our studies identify the transient receptor potential canonical-1 (TRPC1) ion channel as a key component of responses to hypoxia in breast cancer cells. This regulation includes control of specific epithelial to mesenchymal transition (EMT) events and hypoxia-mediated activation of signalling pathways such as activation of the EGFR, STAT3 and the autophagy marker LC3B, through hypoxia-inducible factor-1α (HIF1α)-dependent and -independent mechanisms. TRPC1 regulated HIF1α levels in PTEN-deficient MDA-MB-468 and HCC1569 breast cancer cell lines. This regulation arises from effects on the constitutive translation of HIF1α under normoxic conditions via an Akt-dependent pathway. In further support of the role of TRPC1 in EMT, its expression is closely associated with EMT-and metastasisrelated genes in breast tumours, and is enhanced in basal B breast cancer cell lines. TRPC1 expression is also significantly prognostic for basal breast cancers, particularly those classified as lymph node positive. The defined roles of TRPC1 identified here could be therapeutically exploited for the control of oncogenic pathways in breast cancer cells.

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Section: +mentioning

confidence: 99%

TRPC1 is a differential regulator of hypoxia-mediated events and Akt signalling in PTEN-deficient breast cancer cells

Azimi

Milevskiy

Kaemmerer

et al. 2017

Journal of Cell Science

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“…It is also showed that breast cancers of the basal subtype are characterized by elevated levels of SPCA1. The SPCA1 inhibition in the basal-like breast cancer cell line MDA-MB-231 produced pronounced changes in cell proliferation, morphology, as well as regulation of calciumdependent enzymes located in the secretory pathway [60]. However, at present, the contribution of SPCAs in other disorders remained largely unexplored and further exploration is strongly needed.…”

Section: Ca 2? Homeostasis With Oxidative Stress and Apoptosismentioning

confidence: 98%

“…Pronounced alterations in cell proliferation, morphology, regulation of calcium-dependent enzymes located in the secretory pathway, and the processing of insulin-like growth factor receptor (IGF1R) [60] Incomplete suppression by siRNA interference in the N2a cell line and hippocampal cultured neurons Delayed differentiation and impaired neural polarity [30] Total suppression by siRNA interference in hippocampal neurons Apoptosis [30] Partial knockdown of rat SPCA1 gene in the chimeric liver-derived cell line WIF-B…”

Section: Future Directionsmentioning

confidence: 99%

The Role of the Golgi-Resident SPCA Ca2+/Mn2+ Pump in Ionic Homeostasis and Neural Function

2011

Neurochem Res

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Recent evidence highlights the functional importance of the Golgi apparatus (GA) in neurological diseases. The functions of the mammalian GA, in addition to the processing and transport of cargo, also include ionic homeostasis. Besides Ca²⁺-release channels which serves GA as an agonist-sensitive intracellular Ca²⁺ store, and Ca²⁺-binding proteins, the GA contains Ca²⁺-uptake mechanisms consisting of the well-known sarco-endoplasmic reticulum Ca²⁺-transport ATPases and the much less characterized secretory-pathway Ca²⁺-transport ATPases (SPCA). SPCA can transport both Ca²⁺ and Mn²⁺ into the Golgi lumen and therefore is involved in the cytosolic and intra-Golgi Ca²⁺ and Mn²⁺ homeostasis. It has shown that both of the mRNA and protein of SPCAs are highly expressed in brain. In addition, brain is the region with the highest activity of SPCA isoforms, which may be related to the involvement of Ca²⁺ and Mn²⁺ homeostasis in neural functions. In this review, we compile some recent findings showing that the SPCA isoform plays a much more important role in intracellular ionic homeostasis than previously anticipated and illustrating the involvement of SPCA isoforms in certain neurophysiological or neuropathological process. We are interested in gaining insight into the intricate role of the SPCA pumps to explain the GA-specific functions in neurological disorders.

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“…In some cases, Hailey-Hailey skin lesions eventually evolve into squamous carcinomas [185]. Of interest, recently an association between cancer and SPCA1 has been reported, although of opposite nature: significantly elevated SPCA1 levels have been described in basal-like breast cancers, while the inhibition of SPCA1 in a breast cancer cell line led to a pronounced alteration in cell growth, morphology and in the processing of insulin-like growth factor receptors, with their functional levels significantly reduced [186]. Thus, changes in SPCA1 expression can affect, presumably by altering GA (but also secretory vesicles, see below) Ca 2?…”

Section: The Golgi Apparatusmentioning

confidence: 99%

Intracellular organelles in the saga of Ca2+ homeostasis: different molecules for different purposes?

Zampese

Pizzo

2011

Cell. Mol. Life Sci.

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An increase in the concentration of cytosolic free Ca(2+) is a key component regulating different cellular processes ranging from egg fertilization, active secretion and movement, to cell differentiation and death. The multitude of phenomena modulated by Ca(2+), however, do not simply rely on increases/decreases in its concentration, but also on specific timing, shape and sub-cellular localization of its signals that, combined together, provide a huge versatility in Ca(2+) signaling. Intracellular organelles and their Ca(2+) handling machineries exert key roles in this complex and precise mechanism, and this review will try to depict a map of Ca(2+) routes inside cells, highlighting the uniqueness of the different Ca(2+) toolkit components and the complexity of the interactions between them.

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Golgi Calcium Pump Secretory Pathway Calcium ATPase 1 (SPCA1) Is a Key Regulator of Insulin-like Growth Factor Receptor (IGF1R) Processing in the Basal-like Breast Cancer Cell Line MDA-MB-231

Cited by 76 publications

References 52 publications

TRPC1 is a differential regulator of hypoxia-mediated events and Akt signalling in PTEN-deficient breast cancer cells

TRPC1 is a differential regulator of hypoxia-mediated events and Akt signalling in PTEN-deficient breast cancer cells

The Role of the Golgi-Resident SPCA Ca2+/Mn2+ Pump in Ionic Homeostasis and Neural Function

Intracellular organelles in the saga of Ca2+ homeostasis: different molecules for different purposes?

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