Emerging roles of the single EF-hand Ca2+ sensor tescalcin in the regulation of gene expression, cell growth and differentiation

Kolobynina, Ksenia; Solovyova, Valeria V.; Levay, Konstantin; Rizvanov, Albert A.; Slepak, Vladlen Z.

doi:10.1242/jcs.191486

Cited by 24 publications

(20 citation statements)

References 67 publications

(112 reference statements)

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“…The sequence similarity between TESC and calcineurin B-homologous proteins 1 and 2 (CHP1 and CHP2) is substantial [27,28]. CHP1 is expressed ubiquitously in all tissues [29,30], whereas CHP2 is expressed in the small intestine and several cancers, including hepatic carcinoma, leukemia, breast cancer, and ovarian cancer [31][32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

TESC Promotes TGF-α/EGFR-FOXM1-Mediated Tumor Progression in Cholangiocarcinoma

Hsieh

Chu

Lin

et al. 2020

Cancers

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Cholangiocarcinoma is a relatively uncommon but highly lethal malignancy. Improving outcomes in patients depends on earlier diagnosis and appropriate treatment; however, no satisfactory diagnostic biomarkers or targeted therapies are currently available. To address this shortcoming, we analyzed the transcriptomic datasets of cholangiocarcinoma from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and found that TESC is highly expressed in cholangiocarcinoma. Elevated cellular levels of TESC are correlated with larger tumor size and predict a poor survival outcome for patients. Knockdown of TESC via RNA interference suppresses tumor growth. RNA-sequencing analysis showed that silencing of TESC decreases the level of FOXM1, leading to cell cycle arrest. Correlation analysis revealed that the cellular level of TESC is correlated with that of FOXM1 in cholangiocarcinoma patients. We further observed that upon TGF-α induction, TESC is upregulated through the EGFR-STAT3 pathway and mediates TGF-α-induced tumor cell proliferation. In vivo experiments revealed that knockdown of TESC significantly attenuates tumor cell growth. Therefore, our data provide novel insight into TESC-mediated oncogenesis and reveal that TESC is a potential biomarker or serves as a therapeutic target for cholangiocarcinoma.

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Section: Discussionmentioning

confidence: 99%

TESC Promotes TGF-α/EGFR-FOXM1-Mediated Tumor Progression in Cholangiocarcinoma

Hsieh

Chu

Lin

et al. 2020

Cancers

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“…Tescalcin (TESC), also known as calcineurin B homologous protein 3 (CHP3), was first discovered as a differentially expressed gene in the development of embryonic mouse testis [ 6 ]. Since TESC contained an EF-hand motif that is characteristic of a large family of Ca 2+ -binding proteins, it is supposed to be involved in cell growth and differentiation [ 7 ]. Previous studies have proved that abnormal expression of the TESC was associated with many types of malignant tumors including melanoma, gastric cancer, renal cell carcinoma, and colorectal cancer [ 8 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

Tescalcin promotes highly invasive papillary thyroid microcarcinoma by regulating FOS/ERK signaling pathway

et al. 2022

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Background Part of papillary thyroid microcarcinoma (PTMC) has a high risk of tumor invasion and metastasis, which may occur in the regional lymph node metastasis or distant metastasis, severely threatening the life of patients. Invasion and metastasis are tightly involved in the proliferation, migration and invasion in cancer. This study aimed to investigate the role of tescalcin (TESC) in the proliferation, migration and invasion of PTMC. Methods The expressions of TESC in PTMC tissues and cells were detected by immunohistochemistry or qRT-PCR. Then, TPC-1 and BHT101 cells transfected with TESC-RNAi were used for the transcriptome sequencing. The proliferation, apoptosis, migration and invasion of TPC-1 and BHT101 cells were detected by CCK-8, colony formation, flow cytometric assay, transwell migration and scratch test. Moreover, TESC-RNAi transfected TPC-1 and BHT101 cells were subcutaneously injected into mice. Tumor volume and weight were calculated, and the positive rate of Ki-67 was determined by immunohistochemistry. Finally, the levels of c-Fos, ERK1/2 and p-ERK1/2 were determined by western blot. Results The expressions of TESC in PTMC tissues and cell lines were prominently enhanced. Transcriptome sequencing results showed that c-Fos was decreased in TPC-1 and BHT101 cells transfected with TESC-RNAi, which was associated with multiple different signaling pathways including the MAPK signaling pathway. Furthermore, TESC promoted the progress of PTMC by regulating the expression of c-Fos, which might be associated with the ERK signaling pathway. Conclusions TESC promoted the growth and metastasis of PTMC through regulating c-Fos/ERK1/2.

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“…Mielenz and Gunn‐Moore reviewed functions of swiprosin (EFHD_DM). Kolobynina et al reviewed the functions of P22 . Sole et al reviewed P22 .…”

Section: Ef‐hand Proteinsmentioning

confidence: 99%

Structural and functional diversity of EF‐hand proteins: Evolutionary perspectives

Kawasaki

Kretsinger

2017

Protein Science

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We have classified 865 sequences of EF-hand proteins from five proteomes into 156 subfamilies. These subfamilies were put into six groups. Evolutionary relationships among subfamilies and groups were analyzed from the inferred ancestral sequence for each subfamily. CTER, CPV, and PEF groups arose from a common EF-lobe (pair of adjacent EF-hands). They have two or more EF-lobes; the relative positions of their EF-lobes differ from each other. Comparisons of the ancestral sequences and the inferred structures of the EF-lobes of these groups indicate that the mutual positions of EF-lobes were established soon after divergence of an EF-lobe for each group and before the duplication and fusion of EF-lobe gene(s). These ancestral sequences reveal that some subfamilies in low similarity and isolated groups did not evolve from the EF-lobe precursor, even if their conformations are similar to the canonical EF-hand. This is an example of convergent evolution.

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Emerging roles of the single EF-hand Ca2+ sensor tescalcin in the regulation of gene expression, cell growth and differentiation

Cited by 24 publications

References 67 publications

TESC Promotes TGF-α/EGFR-FOXM1-Mediated Tumor Progression in Cholangiocarcinoma

TESC Promotes TGF-α/EGFR-FOXM1-Mediated Tumor Progression in Cholangiocarcinoma

Tescalcin promotes highly invasive papillary thyroid microcarcinoma by regulating FOS/ERK signaling pathway

Structural and functional diversity of EF‐hand proteins: Evolutionary perspectives

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