Calpain in Breast Cancer: Role in Disease Progression and Treatment Response

Storr, Sarah J.; Thompson, Nicola; Pu, Xuan; Zhang, Yimin; Martin, Stewart G.

doi:10.1159/000430464

Cited by 44 publications

(41 citation statements)

References 97 publications

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“…Two members of the calpain family µ-calpain (calpain-1) and m-calpain (calpain-2) are ubiquitously expressed (11 (12). Investigations have demonstrated that calpain has a role in breast cancer progression, prognosis and treatment response, thus it is considered as a potential anticancer target (13). Furthermore, calpain activity is aberrantly higher in breast cancer tissues compared with normal breast tissues, and its expression correlates with metastatic phenotypic characteristics and increased invasive properties of tumors (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Fibronectin induces epithelial-mesenchymal transition in human breast cancer MCF-7 cells via activation of calpain

Yang

Cao

et al. 2017

Oncology Letters

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Abstract. Fibronectin (FN) is a primary component of the mammary mesenchymal compartment and undergoes dramatic changes during breast cancer development. Increased FN expression is associated with an invasive and metastatic breast cancer phenotype. The present study demonstrated that FN causes an epithelial-mesenchymal transition (EMT)-like morphological change in MCF-7 breast cancer cells. FN stimulation caused the downregulation of epithelial markers E-cadherin and tight junction protein ZO-1, and the upregulation of mesenchymal markers N-cadherin and vimentin. Additionally, FN promoted cell migration and invasion in MCF-7 cells, with increased expression of calpain-2 and proteolysis of focal adhesion kinase 1 (FAK), indicating calpain activation. Notably, the FN induced changes in morphology and EMT markers were reversed with the treatment of calpain-specific inhibitors, calpain inhibitor I (N-acetyl-L-leucyl-L-leucyl-L-norleucinal), calpeptin and calpain inhibitor IV. Meanwhile, the effects of FN on cell migration and invasion, as well as FAK proteolysis were markedly suppressed by calpain inhibitors. Taken together, the results of the present study indicate that calpain plays an essential role in FN-induced EMT response, and that targeting calpain signaling may be a potential strategy to reduce breast cancer metastasis.

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Section: Introductionmentioning

confidence: 99%

Fibronectin induces epithelial-mesenchymal transition in human breast cancer MCF-7 cells via activation of calpain

Yang

Cao

et al. 2017

Oncology Letters

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“…It is worth noting that the physiological functions of calpains are extensive, including regulation of apoptosis [31], cell migration [32], AR co-factor activation [33], and cell-to-cell communication via microparticle biogenesis [34,35] so on. Further exploration of the profound influence of triptolide on systematic function of cells or humans is still needed.…”

Section: Discussionmentioning

confidence: 99%

Alteration of Androgen Receptor Protein Stability by Triptolide in LNCaP Cells

Liu

Liao

et al. 2018

Medicina

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Background and Objective: Although triptolide was effective for prostate cancer (PCa), the mechanism is still unclear. Androgen receptor (AR) plays a large role in the development and progression of PCa, even after castration. The present study aimed at investigating the effects of triptolide on AR protein stability and the possible mechanism. Materials and Methods: By blocking protein synthesis with cycloheximide (CHX), the effect of triptolide on AR protein stability was investigated with western blot assay. The potential role of calpains in triptolide reduced AR protein stability was investigated with calpain inhibitor and Ca2+ chelator. Results: Triptolide down-regulated AR protein level when protein synthesis was blocked by CHX, demonstrating the decrease of AR protein stability. The AR protein level was restored when the cells were co-treated with triptolide and calpain inhibitor or Ca2+ chelator, indicating the important role of calpains. Conclusions: The results indicate that triptolide can activate calpain via promoting intracellular Ca2+ accumulation, and thus decrease the stability of AR protein, subsequently resulting in the breakdown of the AR protein in LNCaP cells. This work provides an experimental basis and evidence to elucidate the anti-PCa mechanisms of triptolide.

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“…Calpains were identified to be involved in various biological processes, including cytoskeleton remodeling, signal transduction and cell apoptosis (6–8). Currently, 16 family members have been identified (9), which are classified into two types: The classical calpains and the non-classical calpains (4,5,10–15). Due to slight variations in their structure, the various calpains were identified to be associated with various physiological activities.…”

Section: Introductionmentioning

confidence: 99%

Decreased calpain 6 expression is associated with tumorigenesis and poor prognosis in HNSCC

et al. 2017

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Calpains are a family of intracellular cysteine proteases involved in various biological processes. Previously, the family was identified to have abnormal expression in several types of malignant tumor. Calpain 6 was less well known; however, it was recently identified to be involved in the carcinogenesis of certain types of malignant tumor. However, the expression of calpain 6 in head and neck squamous cell carcinoma (HNSCC) remains unclear. A total of six datasets from the Gene Expression Omnibus (GEO) was analyzed and an association between calpain 6 expression levels and HNSCC was identified, with the expression of calpain 6 observed to be significantly decreased in HNSCC (P<0.01). However, the expression of calpain 6 may vary between distinct tumor stages of HNSCC. Furthermore, calpain 6 expression was positively associated with the survival rate in patients with HNSCC (P<0.05), with increased expression of calpain 6 associated with an improved survival outcome. Calpain 6 expression was analyzed using an HNSCC tissue microarray and these results were consistent with the statistical analysis of the bioinformatics data from the GEO, indicating that calpain 6 may be a tumor suppressor protein in HNSCC.

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Calpain in Breast Cancer: Role in Disease Progression and Treatment Response

Cited by 44 publications

References 97 publications

Fibronectin induces epithelial-mesenchymal transition in human breast cancer MCF-7 cells via activation of calpain

Fibronectin induces epithelial-mesenchymal transition in human breast cancer MCF-7 cells via activation of calpain

Alteration of Androgen Receptor Protein Stability by Triptolide in LNCaP Cells

Decreased calpain 6 expression is associated with tumorigenesis and poor prognosis in HNSCC

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