HspB5 correlates with poor prognosis in colorectal cancer and prompts epithelial-mesenchymal transition through ERK signaling

Li, Qinghua; Wang, Yanlan; Lai, Yuexing; Xu, Ping; Yang, Zhiwen

doi:10.1371/journal.pone.0182588

Cited by 24 publications

(33 citation statements)

References 33 publications

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“…Similar results were obtained by Li et al (2017) in a study conducted on 70 samples of colorectal cancer; they found up-regulation of αB-crystallin and its positive association with tumour stage and level of matrix metalloproteinase-7 (MMP-7). They also provided evidence that EMT induced by αB-crystallin may be regulated by ERK, PI3K and p38 signaling pathways [100].…”

Section: Annals Of Agricultural and Environmental Medicinesupporting

confidence: 83%

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 Medicinesupporting

confidence: 83%

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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“…These results indicate that inhibition of ANXA9 expression levels in HcT116 cells may induce suppression of AdMA17 and MMP-9 expression levels, but increase the TIMP-1 expression level contributing to the weakness of tumor cells in invasion and migration (26,32). Epithelial-mesenchymal transition (EMT) contributes to the invasion and migration of cRc (33). E-cadherin and N-cadherin are important in EMT of cRc (34,35).…”

Section: Discussionmentioning

confidence: 99%

Annexin A9 promotes invasion and metastasis of colorectal cancer and predicts poor prognosis

Bian

Gào

et al. 2018

Int J Mol Med

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Annexin A9 (ANXA9), a member of annexin family, has been reported be associated with colorectal cancer (CRC) carcinogenesis. However, the clinical significance of ANXA9 in CRC, particularly its correlation to invasion and metastasis remains ambiguous. The aim of the present study was to investigate the significance of ANXA9 in CRC and understand the molecular mechanism of ANXA9 in CRC invasion and metastasis. Expression levels of the ANXA9 protein in CRC tissues were detected using immunohistochemistry (IHC), and the clinical and prognostic value of ANXA9 was investigated. ANXA9‑siRNA was utilized to investigate the effect and molecular mechanism of ANXA9 in HCT116 cells. The IHC result demonstrated that the positivity rate of the ANXA9 protein in CRC tissue was significantly higher than that in adjacent mucosa (P<0.05), which was consistent with the western blot results. ANXA9 protein expression levels are associated with invasion depth and lymphatic metastasis. Furthermore, patients with ANXA9‑positive expression demonstrated a poor prognosis and ANXA9 was an independent risk factor for survival (P<0.05). After inhibiting ANXA9 in HCT116 cells, the activity and metastatic and invasion capacity of cells decreased significantly, and expression levels of ADAM metallopeptidase domain 17 and matrix metallopeptidase 9 were significantly downregulated, while the expression levels of tissue inhibitors of metalloproteinases‑1 and E‑cadherin were upregulated (P<0.05). Thus, positive ANXA9 expression may present as a novel marker for predicting poor prognosis in CRC patients, and ANXA9 may promote the invasion and metastasis of CRC by regulating invasion and metastasis‑associated genes.

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“…[10][11][12] It is a member of small heat shock protein family and functions as a molecular chaperon in order to prevent the aggregation of proteins denatured by stresses, such as radiation and heat shock. 10 Recent studies have reported that increased expression of CRYAB renders several highly invasive and metastatic solid tumor cells, [13][14][15][16] whereas degradation and phosphorylation of CRYAB during enterovirus infection facilitates viral replication and induces viral pathogenesis. 17 Interestingly, several studies have reported that CRAYB plays protective and therapeutic roles in the development of neuroinflammation induced by injury, infection, neurodegeneration, and autoimmunity.…”

Section: Introductionmentioning

confidence: 99%

Small heat shock protein CRYAB inhibits intestinal mucosal inflammatory responses and protects barrier integrity through suppressing IKKβ activity

Guo

Huang

et al. 2019

Mucosal Immunology

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Alpha B-crystallin (CRYAB) is an important member of the small heat shock protein family, and plays a protective and therapeutic role in neurological inflammation. CRYAB expression was assessed in cultured HT29 and Caco-2 cells and inflamed mucosa of patients with inflammatory bowel disease (IBD) and colitis models in mice. Lentivirus-overexpressing and CRSIPR/Cas9 systems were used in different cells to upregulate and silence CRYAB expression, respectively. Cell permeable recombined fusion protein TAT-CRYAB was injected intraperitoneally into dextran sulfate sodium (DSS)-or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice to assess its anti-inflammatory effects. CRYAB was found to be significantly decreased in the inflamed mucosa from IBD patients and DSS-induced colitis in mice, and negatively correlated with the levels of TNF-α and IL-6, respectively. Enforced expression of CRYAB suppressed expression of proinflammatory cytokines (e.g., TNF-α, IL-6, IL-1β, and IL-8) via inhibiting the IKK complex formation, whereas lack of CRYAB expression markedly enhanced proinflammatory responses. Consistently, administration of TAT-CRYAB fusion protein significantly alleviated DSS-or TNBS-induced colitis in mice and protected intestinal barrier integrity. CRYAB regulates inflammatory response in intestinal mucosa by inhibiting IKKβ-mediated signaling and may serve as a novel therapeutic approach in the treatment of IBD.

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HspB5 correlates with poor prognosis in colorectal cancer and prompts epithelial-mesenchymal transition through ERK signaling

Cited by 24 publications

References 33 publications

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

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

Annexin A9 promotes invasion and metastasis of colorectal cancer and predicts poor prognosis

Small heat shock protein CRYAB inhibits intestinal mucosal inflammatory responses and protects barrier integrity through suppressing IKKβ activity

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