A review of S100 protein family in lung cancer

J Cellular Molecular Medi

Zhang

et al. 2018

Gastric cancer (GC) is a malignancy of the lining of the stomach and is prone to distant metastasis, which involves a variety of complex molecules. The S100 proteins are a family of calcium‐binding cytosolic proteins that possess a wide range of intracellular and extracellular functions and play pivotal roles in the invasion and migration of tumour cells. Among these, S100A10 is known to be overexpressed in GC. Lysine succinylation, a recently identified form of protein post‐translational modification, is an important regulator of cellular processes. Here, we demonstrated that S100A10 was succinylated at lysine residue 47 (K47), and levels of succinylated S100A10 were increased in human GC. Moreover, K47 succinylation of S100A10 was stabilized by suppression of ubiquitylation and subsequent proteasomal degradation. Furthermore, carnitine palmitoyltransferase 1A (CPT1A) was found to function as a lysine succinyltransferase that interacts with S100A10. Succinylation of S100A10 is regulated by CPT1A, while desuccinylation is regulated by SIRT5. Overexpression of a succinylation mimetic mutant, K47E S100A10, increased cell invasion and migration. Taken together, this study reveals a novel mechanism of S100A10 accumulation mediated by succinylation in GC, which promotes GC progression and is regulated by the succinyltransferase CPT1A and SIRT5‐mediated desuccinylation.

Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

CPT1A‐mediated succinylation of S100A10 increases human gastric cancer invasion

J Cellular Molecular Medi

Zhang

et al. 2018

“…Dysregulated expression of multiple members of the S100 protein family is considered a common feature in lung carcinoma, but the effects of S100A14 in lung adenocarcinoma have not been reported. In this project, we used immunohistochemical staining to detect expression of the S100A14 protein in 208 cases of lung adenocarcinoma and adjacent normal lung tissues.…”

Section: Discussionmentioning

confidence: 99%

“…17 In addition, 12-O-tetradecanoylphorbol-13-acetate can increase the level of S100A14 in a KLF4-dependent manner and promote the migration of breast invasive ductal carcinoma cells. 18 Dysregulated expression of multiple members of the S100 protein family is considered a common feature in lung carcinoma, 19 but the effects of S100A14 in lung adenocarcinoma have not been reported. In this project, we used immunohistochemical staining to detect expression of the S100A14 protein in 208 cases of lung adenocarcinoma and adjacent normal lung tissues.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of S100A14 contributes to malignant progression and predicts poor prognosis of lung adenocarcinoma

Ding

et al. 2018

Thoracic Cancer

BackgroundS100A14 is a member of the S100 calcium‐binding protein family that exerts important phenotypic effects on cell proliferation, apoptosis, differentiation, and motility. However, the functional role and potential clinical significance of S100A14 in lung adenocarcinoma has not yet been clarified.MethodsWe analyzed genomic alterations of S100A14 using The Cancer Genome Atlas lung adenocarcinoma genomic dataset. S100A14 displayed significant copy number amplification in lung adenocarcinoma. We detected S100A14 expression in lung adenocarcinoma and analyzed the correlation between S100A14 expression and clinicopathological characteristics.ResultsImmunohistochemical analysis showed that S100A14 expression was obviously upregulated in lung adenocarcinoma tissues compared to matched normal counterparts. Statistical analysis revealed that S100A14 expression strongly correlated with poor differentiation, metastasis, stage, smoking, and EGFR mutation. Furthermore, our data indicated that S100A14 serum levels were higher in lung adenocarcinoma patients than healthy controls. Intriguingly, S100A14 serum levels were related to distant metastasis (P = 0.028). High S100A14 expression was significantly associated with overall (P = 0.0016) and post progression (P = 0.039) survival. In addition, we investigated the biological functions of S100A14 in lung adenocarcinoma cell lines. The results demonstrated that S100A14 promoted cell migration and invasion of SPCA1 and Glc‐82 cells.ConclusionsS100A14 increases the motility of lung adenocarcinoma cells, and might be a diagnostic and prognostic serum biomarker and potential therapeutic target for lung adenocarcinoma.

“…Some members in this group are found to be multifunctional proteins that are expressed differently in a variety of cell types and get involved in the regulation of inflammatory response, cellular activities like cell differentiation [10,11]. Through binding target proteins or genes (e.g., p53), a number of S100 members could also fulfill kinds of intra-or extra-cellular functions [12]. Expression of several S100 proteins such as S100A4, S100B, and S100A6 are abnormal in some cancers, including lung carcinoma [13,14].…”

Section: Introductionmentioning

confidence: 99%

S100A2 induces the growth of Calu-6 Lung Cancer Cells via apoptosis inhibition, invasion enhancement and promoting cell division

Liang

Thakur³

2019

Preprint

Self Cite

Background S100 calcium binding protein A2 (S100A2) has been confirmed to have an abnormal expression in lung cancer and is associated with a better disease-free internal of lung cancer patients.Our previous studies on S100A2 in lung cancer concentrated on the clinical roles of this protein in lung cancer, finding that S100A2 increasingly expressed in the sera, tissues and plural effusion of lung cancer patients. This study emphasizes its value in the lung cancer cell line.Methods We constructed a S100A2 expression lentivirus vector, then transfected it and blank vector into the Calu-6 lung cancer cell line respectively. After the successful transfection, (which was confirmed by RT-PCR and Western-blot), we used MTT, transwell and flow cytometric analysis to compare the differences in cell proliferation, cell migration, cell invasion, cell apoptosis and cell cycle among the three groups (Calu-6, Calu/neo, Calu-6/S100A2).Results Calu-6 lung cancer cells showed a shift from G1 to S phase after being transfected with S100A2, compared with the control groups. Additionally, Calu-6/S1000A2 cells had enhanced abilities of invasion and down-abilities of apoptosis in contrast with the blank groups (P<0.05). However, there were no significant difference among these three group in the cell behaviors of migration and proliferation (P>0.05). ConclusionOur results firstly indicate that S100A2 has a positive influence on the biological characteristics of Calu-6 lung cancer cell line, including cell division, invasion and apoptosis inhibition.It may play a significant role in the genesis and progression of lung cancer.