Sorcin Induces a Drug-Resistant Phenotype in Human Colorectal Cancer by Modulating Ca2+ Homeostasis

Maddalena, Francesca; Laudiero, Gabriella; Piscazzi, Annamaria; Secondo, Agnese; Scorziello, Antonella; Lombardi, Valentina; Matassa, Danilo Swann; Fersini, Alberto; Neri, Vincenzo; Esposito, Franca; Landriscina, Matteo

doi:10.1158/0008-5472.can-11-2172

Cited by 83 publications

(77 citation statements)

References 43 publications

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“…Specific siRNAs targeting chemoresistant genes designed using RNAi technology have shown considerable potential in reversing MDR (Maddalena et al, 2011;Li et al, 2012;Zhao et al, 2012;Yin et al, 2012). In the current study, we constructed recombinant lentivirus containing siRNA targeting GST-π and polβ genes.…”

Section: Discussionmentioning

confidence: 99%

Roles of GST-π and polβ Genes in Chemoresistance of Esophageal Carcinoma Cells

Tang

Xing²,

Li³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Section: Discussionmentioning

confidence: 99%

Roles of GST-π and polβ Genes in Chemoresistance of Esophageal Carcinoma Cells

Tang

Xing²,

Li³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Recent reports indicate that Sorcin localizes to the nucleus, the ER and cytoplasmic vesicles, and plasma membrane of 3T3-L1 fibroblasts, and plays important roles in Ca2+-loaded vesicle trafficking and calcium homeostasis 2,3) . Sorcin increases the accumulation of Ca2+ in the ER, preventing ER stress, and is upregulated in response to ER stress 4) . The ectopic overexpression of Sorcin in 3T3-L1…”

Section: Introductionmentioning

confidence: 99%

“…The presence of Sorcin-containing, calcium-rich ER vesicles at the cleavage furrow and the midbody strongly links calcium signaling to vesicular trafficking and mitosis 4) . Sorcin over-expression has been reported in multidrug-resistant leukemia cells, and the ectopic over-expression of Sorcin in K562 cells leads to be significantly reduced cytosolic calcium levels and an increased cellular resistance to apoptosis 5,6) .…”

Section: Introductionmentioning

confidence: 99%

Sorcin Expression in the Epiphyseal Growth Plates of Mice

Kawai

Liu

Hattori

et al. 2016

J. Hard Tissue Biology.

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Sorcin is a small calcium-binding protein that is widely expressed in many tissues. Sorcin regulates cardiac myocyte apoptosis by modulating mitochondrial Ca 2+ cycling and regulates fibroblast cell cycling and apoptosis via Ca 2+ signaling through the endoplasmic reticulum (ER). During endochondral ossification, some chondrocytes undergo apoptosis after their terminal differentiation; however, Sorcin's expression in these cells has not been characterized. Here we examined Sorcin's gene expression in the chondrocytes derived from mouse growth plate by reverse transcription PCR (RT-PCR), and its protein localization in the chondrocytes of femoral growth plate using immunohistochemistry. Sorcin protein was detected in the chondrocytes, and was particularly abundant in the cytoplasm and nuclei of proliferative zone chondrocytes and in the nuclei of hypertrophic chondrocytes. Apoptotic analysis of the growth plate revealed that many of the hypertrophic chondrocytes undergo the DNA fragmentation. We report for the first time the localization of Sorcin in the epiphyseal growth plate in which one of the apoptotic phenomenon was detected.

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“…Remarkably, TRAP1 regulates, together with TBP7, the ubiquitination of Sorcin isoform B; consequently, Sorcin expression levels are decreased upon TRAP1 interference, as a consequence of increased ubiquitination [4]. The 22kDa isoform of Sorcin, which is the most abundant cellular isoform and is up-regulated in about 50% of human CRCs, is not a TRAP1 interacting protein [19]; however, in human CRCs, TRAP1 expression significantly correlates with the protein levels of 22kDa Sorcin [20]. Indeed, 22kDa Sorcin is an ER-resident protein up-regulated in conditions of ER stress and responsible for enhancing the accumulation of Ca 2+ in the ER, thus preventing ER stress.…”

mentioning

confidence: 99%

“…Indeed, 22kDa Sorcin is an ER-resident protein up-regulated in conditions of ER stress and responsible for enhancing the accumulation of Ca 2+ in the ER, thus preventing ER stress. Its silencing favors the activation of caspase-12 and Grp78/ BiP in response to stress and induces apoptosis through the mitochondrial pathway [20]. Based on such evidence, it is reasonable to hypothesize that both Sorcin isoforms are involved in regulating Ca 2+ homeostasis in separate cell compartments and that this function is relevant for their antiapoptotic activities in tumor cells.…”

mentioning

confidence: 99%

ER stress protection in cancer cells: the multifaceted role of the heat shock protein TRAP1

Matassa

Arzeni

Landriscina

et al. 2014

Endoplasmic Reticulum Stress in Diseases

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Abbreviations TRAPis involved in ER stress protection of cancer cellsTRAP1 (Tumour Necrosis Factor Receptor-Associated Protein 1) is a molecular chaperone, member of the HSP90 family, that contributes to the overall survival of cancer cells and is up-regulated in most tumour types (reviewed in 1). A large body of literature demonstrates that TRAP1 is part of a pro-survival signalling pathway aimed at evading the toxic effects of oxidants and anticancer drugs and plays a role in protecting mitochondria against apoptotic stimuli (reviewed in 2). However, whether its roles are uniformly oncogenic or not is now a matter of intense debate. Interestingly, Yoshida and colleagues [3] propose a more subtle reading of TRAP1 roles in the regulation of cellular metabolism and its impact on tumorigenesis. In fact, an inverse correlation between TRAP1 expression and tumor stage in cervical, bladder, and clear cell renal cell carcinoma was demonstrated. These conflicting observations on TRAP1 "behaviour" in different biological contexts is strictly related to a specific molecular complex/integrated network in which TRAP1 represents one of the focal nodes.Abstract: TRAP1 is an HSP90 chaperone, upregulated in human cancers and involved in organelles' homeostasis and tumor cell metabolism. Indeed, TRAP1 is a key regulator of adaptive responses used by highly proliferative tumors to face the metabolic stress induced by increased demand of protein synthesis and hostile environments. Besides well-characterized roles in prevention of mitochondrial permeability transition pore opening and in regulating mitochondrial respiration, TRAP1 is involved in novel regulatory mechanisms: i) the attenuation of global protein synthesis, ii) the co-translational regulation of protein synthesis and ubiquitination of specific client proteins, and iii) the protection from Endoplasmic Reticulum stress. This provides a crucial role to TRAP1 in maintaining cellular homeostasis through protein quality control, by avoiding the accumulation of damaged or misfolded proteins and, likely, facilitating the synthesis of selective cancer-related proteins. Herein, we summarize how these regulatory mechanisms are part of an integrated network, which enables cancer cells to modulate their metabolism and to face, at the same time, oxidative and metabolic stress, oxygen and nutrient deprivation, increased demand of energy production and macromolecule biosynthesis. The possibility to undertake a new strategy to disrupt such networks of integrated control in cancer cells holds great promise for treatment of human malignancies.

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Sorcin Induces a Drug-Resistant Phenotype in Human Colorectal Cancer by Modulating Ca2+ Homeostasis

Cited by 83 publications

References 43 publications

Roles of GST-π and polβ Genes in Chemoresistance of Esophageal Carcinoma Cells

Roles of GST-π and polβ Genes in Chemoresistance of Esophageal Carcinoma Cells

Sorcin Expression in the Epiphyseal Growth Plates of Mice

ER stress protection in cancer cells: the multifaceted role of the heat shock protein TRAP1

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