Targeting Ca2+ signalling through phytomolecules to combat cancer

Singh, Jyoti; Hussain, Yusuf; Luqman, Suaib; Meena, Abha

doi:10.1016/j.phrs.2019.104282

Cited by 13 publications

(8 citation statements)

References 193 publications

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“…Intracellular free Ca 2+ , acts as the second messenger, is essential for multiple cellular functions including invasion and migration [10]. Our previous study reasoned that CRT regulated intracellular free Ca 2+ in PC via Integrin/EGFR-ERK/MAPK, which played an important role in EGF-induced EMT.…”

Section: Crt Silencing Inhibited Tg-induced Emt In Vitromentioning

confidence: 98%

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Calreticulin promotes EMT in pancreatic cancer via mediating Ca2+ dependent acute and chronic endoplasmic reticulum stress

Sheng

Wang

Tang

et al. 2020

J Exp Clin Cancer Res

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Background Our previous study showed that calreticulin (CRT) promoted EGF-induced epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC) via Integrin/EGFR-ERK/MAPK signaling. We next investigated the novel signal pathway and molecular mechanism involving the oncogenic role of CRT in PC. Methods We investigated the potential role and mechanism of CRT in regulating intracellular free Ca2+ dependent acute and chronic endoplasmic reticulum stress (ERS)-induced EMT in PC in vitro and vivo. Results Thapsigargin (TG) induced acute ERS via increasing intracellular free Ca2+ in PC cells, which was reversed by CRT silencing. Additionally, CRT silencing inhibited TG-induced EMT in vitro by reversing TG-induced changes of the key proteins in EMT signaling (ZO-1, E-cadherin and Slug) and ERK/MAPK signaling (pERK). TG-promoted cell invasion and migration was also rescued by CRT silencing but enhanced by IRE1α silencing (one of the key stressors in unfolded protein response). Meanwhile, CRT was co-immunoprecipitated and co-localized with IRE1α in vitro and its silencing led to the chronic ERS via upregulating IRE1α independent of IRE1-XBP1 axis. Moreover, CRT silencing inhibited IRE1α silencing-promoted EMT, including inhibiting the activation of EMT and ERK/MAPK signaling and the promotion of cell mobility. In vivo, CRT silencing decreased subcutaneous tumor size and distant liver metastasis following with the increase of IRE1α expression. A negative relationship between CRT and IRE1α was also observed in clinical PC samples, which coordinately promoted the advanced clinical stages and poor prognosis of PC patients. Conclusions CRT promotes EMT in PC via mediating intracellular free Ca2+ dependent TG-induced acute ERS and IRE1α-mediated chronic ERS via Slug and ERK/MAPK signaling.

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Section: Crt Silencing Inhibited Tg-induced Emt In Vitromentioning

confidence: 98%

“…Intracellular free Ca 2+ is a multifunctional second messenger that controls diverse cellular functions [10]. Recently, we have reported that alteration of CRT mediates intracellular free Ca 2+ concentration in PC cells [4].…”

Section: Introductionmentioning

confidence: 99%

Calreticulin promotes EMT in pancreatic cancer via mediating Ca2+ dependent acute and chronic endoplasmic reticulum stress

Sheng

Wang

Tang

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…CRT silencing inhibited TG-induced EMT in vitro Intracellular Ca 2+ , acts as the second messenger, is essential for multiple cellular functions including invasion and migration 10 . Our previous study reasoned that CRT regulated intracellular Ca 2+ in PC via Integrin/EGFR-ERK/MAPK, which played an important role in EGF-induced EMT.…”

Section: Resultsmentioning

confidence: 99%

Calreticulin Promotes EMT in Pancreatic Cancer via Mediating Ca2+ Dependent Acute and Chronic Endoplasmic Reticulum Stress

Sheng

Wang

Tang

et al. 2020

Preprint

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Background: Our previous study showed that calreticulin (CRT) promoted EGF-induced epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC) via Integrin/EGFR-ERK/MAPK signaling. We next investigated the novel signaling pathway and molecular mechanism involving the oncogenic role of CRT in PC development. Methods: We investigated the potential role and mechanism of CRT in regulating Ca2+ dependent acute and chronic endoplasmic reticulum stress (ERS)-induced EMT in PC in vitro and vivo.Results: Thapsigargin (TG) induced acute ERS via increasing intracellular free Ca2+ in PC cells, which was reversed by CRT silencing. Additionally, CRT silencing inhibited TG-induced EMT in vitro by reversing TG-induced changes of the key proteins in EMT signaling (ZO-1, E-cadherin and Slug) and ERK/MAPK signaling (pERK), and inhibiting TG-promoted cell invasion and migration. Meanwhile, CRT was coimmunoprecipitated with inositol-requiring enzyme 1α (IRE1α, one of the key stressors in unfolded protein response) in vitro and its silencing led to the chronic ERS via upregulating IRE1α but independent of X-box-binding protein 1 (XBP1). Moreover, CRT silencing inhibited IRE1α silencing-promoted EMT, including inhibiting the activation of EMT and ERK/MAPK signaling and the promotion of cell mobility. In addition, CRT silencing decreased subcutaneous tumor size and distant liver metastasis in vivo. Furthermore, a negative relationship between CRT and IRE1α was observed in vivo and in clinical PC samples, which coordinately promoted the advanced clinical stages and poor prognosis of PC patients. Conclusions: CRT promoted EMT in PC via mediating Ca2+ dependent TG-induced acute ERS and IRE1α-mediated chronic ERS via Slug and ERK/MAPK signaling.

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“…The details of structural insights, molecular characterization, physiological functions, pathological defects of STIM and Orai proteins, as well as their dynamic protein-protein interactions that mediated the mediate the activation of SOCE, have been extensively investigated and comprehensively reviewed [ 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 ]. Increasing evidence demonstrating the essential roles of STIM and Orai proteins have made them potential prognostic biomarkers or antitumor therapeutic targets [ 177 , 178 , 179 , 180 , 181 , 182 , 183 ]. Here we updated the recent advances on the importance of STIM/Orai-dependent SOCE in cervical epithelial carcinogenesis and tumor malignant behaviors and the emerging development of SOCE mechanisms as the selective therapeutic target in cervical cancer.…”

Section: Intracellular Ca 2+ Homeostasis and Store-operated Ca 2+ Entry (Soce)mentioning

confidence: 99%

The Important Role of Ion Transport System in Cervical Cancer

Chen

Shen

2021

IJMS

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Cervical cancer is a significant gynecological cancer and causes cancer-related deaths worldwide. Human papillomavirus (HPV) is implicated in the etiology of cervical malignancy. However, much evidence indicates that HPV infection is a necessary but not sufficient cause in cervical carcinogenesis. Therefore, the cellular pathophysiology of cervical cancer is worthy of study. This review summarizes the recent findings concerning the ion transport processes involved in cell volume regulation and intracellular Ca2+ homeostasis of epithelial cells and how these transport systems are themselves regulated by the tumor microenvironment. For cell volume regulation, we focused on the volume-sensitive Cl− channels and K+-Cl− cotransporter (KCC) family, important regulators for ionic and osmotic homeostasis of epithelial cells. Regarding intracellular Ca2+ homeostasis, the Ca2+ store sensor STIM molecules and plasma membrane Ca2+ channel Orai proteins, the predominant Ca2+ entry mechanism in epithelial cells, are discussed. Furthermore, we evaluate the potential of these membrane ion transport systems as diagnostic biomarkers and pharmacological interventions and highlight the challenges.

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Targeting Ca2+ signalling through phytomolecules to combat cancer

Cited by 13 publications

References 193 publications

Calreticulin promotes EMT in pancreatic cancer via mediating Ca2+ dependent acute and chronic endoplasmic reticulum stress

Calreticulin promotes EMT in pancreatic cancer via mediating Ca2+ dependent acute and chronic endoplasmic reticulum stress

Calreticulin Promotes EMT in Pancreatic Cancer via Mediating Ca2+ Dependent Acute and Chronic Endoplasmic Reticulum Stress

The Important Role of Ion Transport System in Cervical Cancer

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