Alpha B‐crystallin promotes the invasion and metastasis of gastric cancer via NF‐κB‐induced epithelial‐mesenchymal transition

Chen, Dehu; Cao, Gan; Qiao, Chunzhong; Liu, Guiyuan; Zhou, Hai-Hua; Liu, Qinghong

doi:10.1111/jcmm.13602

Cited by 58 publications

(54 citation statements)

References 25 publications

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“…αB-crystallin's expression was also studied by Chen previously mentioned studies, showing up-regulation of CRYAB in close correlation with distant metastases and poorer OS. Moreover, high expression of CRYAB promoted epithelial-mesenchymal transition of cancer cells via the NF-κB signaling pathway, thus increasing cells migration and invasion abilities [104].…”

Section: Annals Of Agricultural and Environmental Medicinementioning

confidence: 99%

αB-crystallin as a promising target in pathological conditions – A review

Maksimiuk

Sobiborowicz

Tuzimek

et al. 2020

Ann Agric Environ Med.

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Introduction and objective. αB-crystallin belongs to the ubiquitous family of small heat-shock proteins. It was discovered as a physiological protein of the eye lens, maintaining its liquid-like property. Furthermore, αB-crystallin was proved to playa bipolar role in both physiological and pathophysiological conditions. This review discusses current knowledge about the biology and genetics of αB-crystallin, and summarizes recent advances in understanding its role in ophthalmic and neurological disorders, as well as breast cancer, renal cancer and other malignancies. State of knowledge. α-crystallins are established as important elements of the protein quality control network, and consequently their defects are related to multiple human diseases. New studies highlight αB-crystallin's involvement in proliferative diabetic retinopathy angiogenesis and point out its therapeutic potential in age-related macular degeneration. αB-crystallin is thought to be associated with the disease-causing protein aggregates, leading to its connection with such neurological disturbances as anaplastic astrocytoma, Parkinson disease, aging deficits in the peripheral nervous system and multiple sclerosis. In breast cancer, it was proven to be a marker of aggressive behaviur and cerebral metastases. Strong expression of αB-crystallin promoted growth and migration of clear cell renal cell carcinoma cells and was correlated with lower overall survival rate. Considering other malignancies, its various roles were established in colorectal and gastric cancers, head and neck squamous cell carcinomas and osteosarcomas. Conclusions. Further studies concerning αB-crystallin seem to be enormously promising, as they might improve our understanding of common human pathologies as well as contemporary diagnostics and treatment.

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Section: Annals Of Agricultural and Environmental Medicinementioning

confidence: 99%

αB-crystallin as a promising target in pathological conditions – A review

Maksimiuk

Sobiborowicz

Tuzimek

et al. 2020

Ann Agric Environ Med.

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“…SPOCK1 is an essential driver in several human cancers, [4][5][6][7][8][9][10][11] and some studies have shown that SPOCK1 is critical for DNA repair, cell cycle regulation, metastasis, and apoptosis. The oncogene sparc/ osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1) is a member of the Ca 2+ -binding proteoglycan family.…”

Section: Introductionmentioning

confidence: 99%

“…The oncogene sparc/ osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1) is a member of the Ca 2+ -binding proteoglycan family. SPOCK1 is an essential driver in several human cancers, [4][5][6][7][8][9][10][11] and some studies have shown that SPOCK1 is critical for DNA repair, cell cycle regulation, metastasis, and apoptosis. However, data showing the role of SPOCK1 role in pancreatic cancer tumorigenesis and progression are limited, and the mechanism underlying the differential expression of SPOCK1 is very unclear.…”

Section: Introductionmentioning

confidence: 99%

A potential prognostic marker and therapeutic target: SPOCK1 promotes the proliferation, metastasis, and apoptosis of pancreatic ductal adenocarcinoma cells

Jin

Fang

et al. 2019

J of Cellular Biochemistry

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Pancreatic ductal adenocarcinoma (PDAC), a common malignancy originated from the digestive system worldwide, has a poor clinical outcome. SPOCK1 is a widely investigated member of the Ca2+‐binding proteoglycan family and functions as an essential driver in several cancers. However, the complex regulatory role of SPOCK1 in PDAC is unclear. Bioinformatics analysis predicted an interrelationship between increased SPOCK1 expression and the clinical characteristics of patients with PDAC. The SPOCK1 expression levels in fresh tissue samples were confirmed, and SPOCK1 expression was then knocked down by lentivirus‐mediated short hairpin RNA. Cell proliferation, metastasis, and apoptosis were detected through Cell Counting Kit‐8, colony formation assays, invasion and migration assays, flow cytometric analysis, quantitative real‐time polymerase chain reaction, and Western blot experiment. On the basis of the Cancer Genome Atlas database, we found a significantly higher level of SPOCK1 in PDAC than in adjacent nontumor tissues. Patients with PDAC with high SPOCK1 expression exhibited shorter overall survival time, as well as disease‐free survival time. The knockdown of SPOCK1 significantly decreased the proliferation and metastasis of PCNA‐1 and MIA PaCa‐2 cells. Moreover, the knockdown of SPOCK1 led to cell cycle arrest in G0/G1 phase and increased the proportion of apoptotic PDAC cells by regulating members of the caspase and Bcl‐2 families. Our data proved that SPOCK1 is a critical regulator of tumor proliferation and metastasis in PDAC cells. Therefore, SPOCK1 might be a potential prognostic and therapeutic target molecule in PDAC.

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“…Some of the methylation-driven key regulators were reported to play a significant role in GC. Chen et al showed that overexpression of CRYAB induced EMT, migration, and invasion of gastric cancer cells in vitro and in vivo as well as reversing these phenomena by silencing CRYAB 47 . In addition, they showed strong associations between CRYAB expression and cancer metastasis and survival outcomes in patients.…”

Section: Discussionmentioning

confidence: 99%

“…The increased expressions of the G1 genes (CDO1, CRYAB, FSTL1, and ADHFE1) were significantly associated with poor prognosis as well as advanced tumor stages in multiple datasets. A recent study showed that CRYAB overexpression induced invasion and migration via EMT in gastric cancer cells 47 . FSTL1 expression showed the most consistent and strongest association with both survival and tumor stages within 5 datasets (survival: p-values=0.0002, 1.1×10 -6 , 0.02, 0.0004, and 0.04 for Singapore, ACRG, Australia, Yonsei and SMC datasets, respectively; tumor stages: p-values= 0.0003, 0.01, 6.9×10 -5 , 0.002, and 9.3×10 -5 for HKU, TCGA, Singapore, ACRG, and…”

Section: Clinical Significance Of the Methylation-driven Key Regulatorsmentioning

confidence: 99%

Molecular and cellular heterogeneity of gastric cancer explained by methylation-driven key regulators

Yoo

Chen

Wang

et al. 2020

Preprint

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Gastric cancer (GC) is a heterogeneous disease of diverse genetic, genomic, and epigenetic alterations. Tumor microenvironment (TME) also contributes to the heterogeneity of GC. To investigate GC heterogeneity, we developed an Integrative Sequential Causality Test (ISCT) to identify key regulators of GC by integrating DNA methylation, copy number variation, and transcriptomic data. Applying ISCT to three GC cohorts containing methylation, CNV and transcriptomic data, 11 common methylation-driven key regulators (ADHFE1, CDO1, CRYAB, FSTL1, GPT, PKP3, PTPRCAP, RAB25, RHOH, SFN, and SORD) were identified. Based on these 11 genes, gastric tumors were clustered into 3 clusters which were associated with known molecular subtypes, Lauren classification, tumor stage, and patient survival, suggesting significance of the methylation-driven key regulators in molecular and histological heterogeneity of GC. We further showed that chemotherapy benefit was different in the 3 GC clusters and varied depending on the tumor stage. Both immune/stromal proportions in TME and tumor cell genomic variations contributed to expression variations of the 11 methylation-driven key regulators and to the GC heterogeneity.

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Alpha B‐crystallin promotes the invasion and metastasis of gastric cancer via NF‐κB‐induced epithelial‐mesenchymal transition

Cited by 58 publications

References 25 publications

αB-crystallin as a promising target in pathological conditions – A review

αB-crystallin as a promising target in pathological conditions – A review

A potential prognostic marker and therapeutic target: SPOCK1 promotes the proliferation, metastasis, and apoptosis of pancreatic ductal adenocarcinoma cells

Molecular and cellular heterogeneity of gastric cancer explained by methylation-driven key regulators

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