Calpains and cancer: Friends or enemies?

Moretti, Daniele; Bello, Barbara Del; Allavena, Giulia; Maellaro, Emilia

doi:10.1016/j.abb.2014.09.018

Cited by 62 publications

(74 citation statements)

References 211 publications

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“…Calpains are a family of intracellular Ca 2+ -regulated cysteine proteases, evolutionarily well-conserved from bacteria to mammals [6]. The archetypal members of calpain family, calpain-1 (μ-form) and calpain-2 (m-form), are ubiquitously expressed, while the other members are tissue-specific cysteine proteases that proteolyze different kinds of substrates, leading to their degradation or functional modulation [6].…”

Section: Introductionmentioning

confidence: 99%

“…The archetypal members of calpain family, calpain-1 (μ-form) and calpain-2 (m-form), are ubiquitously expressed, while the other members are tissue-specific cysteine proteases that proteolyze different kinds of substrates, leading to their degradation or functional modulation [6]. Calpain activity has been implicated in several fundamental physiological processes, including cytoskeletal remodeling, migration, proliferation, cell cycle control, survival and apoptosis [7].…”

Section: Introductionmentioning

confidence: 99%

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Elevated Expression of Calpain-4 Predicts Poor Prognosis in Patients with Gastric Cancer after Gastrectomy

Peng

Min

Song

et al. 2016

IJMS

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Calpain-4 belongs to the calpain family of calcium-dependent cysteine proteases, and functions as a small regulatory subunit of the calpains. Recent evidence indicates that calpain-4 plays critical roles in tumor migration and invasion. However, the roles of calpain-4 in gastric tumorigenesis remain poorly understood. Herein, we examined calpain-4 expression by immunohistochemical staining on tissue microarrays containing tumor samples of 174 gastric cancer patients between 2004 and 2008 at a single center. The Kaplan-Meier method was used to compare survival curves, and expression levels were correlated to clinicopathological factors and overall survival. Our data demonstrated that calpain-4 was generally increased in gastric cancer cell lines and primary tumor tissues. High expression of calpain-4 was positively associated with vessel invasion, lymph node metastasis, and advanced TNM (Tumor Node Metastasis) stage. Multivariate analysis identified calpain-4 as an independent prognostic factor for poor prognosis. A predictive nomogram integrating calpain-4 expression with other independent prognosticators was constructed, which generated a better prognostic value for overall survival of gastric cancer patients than a TNM staging system. In conclusion, calpain-4 could be regarded as a potential prognosis indicator for clinical outcomes in gastric cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elevated Expression of Calpain-4 Predicts Poor Prognosis in Patients with Gastric Cancer after Gastrectomy

Peng

Min

Song

et al. 2016

IJMS

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“…5A), though Calpain1 and Calpain2 are constitutively expressed and similar in terms of structure [21]. It has been shown that GAS2DN is able to activate Calpain and inhibits the growth of BCR-ABL + leukemic cells [12,13], because GAS2DN is capable to compete wild-type GAS2 to interact with Calpain2, but fails to suppress the activity of Calpain2.…”

Section: Gas2 Interacts With Calpain2 At Endogenous Levelsmentioning

confidence: 99%

GAS2–Calpain2 axis contributes to the growth of leukemic cells

Sun¹,

Zhou²,

Liu³

et al. 2015

ABBS

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Growth arrest specific 2 (GAS2) modulates cell cycle, apoptosis, and Calpain activity. GAS2-Calpain2 axis is required for the growth of BCR-ABL + hematopoietic cells and chronic myeloid leukemia cells.However, the expression of GAS2 in acute leukemia patients remains unclear and what role GAS2-Calpain2 axis plays in these leukemic cells is not known yet. In this study, GAS2 was found to have significantly higher expression in 16 various leukemic cell lines than in control cells. Using THP-1 cells (from acute myeloid leukemia patient, AML) and Jurkat cells (from acute lymphoid leukemia patient, ALL) as models, we found that GAS2 silence led to elevated Calpain activity, decreased cellular growth, and inhibition of colony-forming cell (CFC) production; and these effects could be rescued by GAS2 re-expression. Moreover, GAS2 silence prevented tumor formation of THP-1 cells in nude mice. In both THP-1 and Jurkat cells, GAS2 interacted with Calpain2 rather than Calpain1. The dominant negative form of GAS2 (GAS2DN, GAS2Δ171-313) had similar effects on leukemic cells through the activation of Calpain. Importantly, Calpain2 silence abolished the proliferation inhibition induced by GAS2 targeting. We also found that GAS2 was aberrantly expressed and Calpain activity was decreased in clinical isolates from acute leukemia patients. Taken together, our results demonstrated the deregulation of GAS2 in both AML and ALL and the requirement of GAS2-Calpain2 axis for the growth of leukemic cells, which will help to understand the molecular pathogenesis of hematological malignancies and possibly to develop novel approaches to treat these deadly diseases.

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“…Calpains are a group of calcium-activated, non-lysosomal neutral cysteine proteases (3). At present, the best-characterized calpain isoforms are calpain-1 (µ-calpain or CAPN1) and calpain-2 (m-calpain or CAPN2), which require µM and mM concentrations of Ca 2+ for their intracellular activity, respectively (3).…”

Section: Introductionmentioning

confidence: 99%

“…At present, the best-characterized calpain isoforms are calpain-1 (µ-calpain or CAPN1) and calpain-2 (m-calpain or CAPN2), which require µM and mM concentrations of Ca 2+ for their intracellular activity, respectively (3). CANP1 and CAPN2 are composed of a distinct large catalytic subunit (80 kDa) and a small common regulatory subunit (28 kDa) (3). Calpains are responsible for the cleavage of a broad spectrum of protein substrates, resulting in the generation of functional fragments rather than total degradation products (4,5).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the protein expression of calpain-1, calpain-2, calpastatin and calmodulin between gastric cancer and normal gastric mucosa

Liu

Zhou

et al. 2017

Oncology Letters

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Abstract. The understanding of molecular mechanisms that are involved in the development and the progression of gastric cancer (GC) are of importance for the diagnosis and treatment. The calpain system, which contains the calpains and the endogenous inhibitor, has been suggested as an important factor in the tumorigenesis and migration of colorectal adenocarcinoma, breast and ovarian cancer, and as a prognostic marker for GC. However, the expression level of calpain system proteins in GC and normal-appearing peritumoral gastric mucosa remain unknown. The present study investigated the expression of calpain-1 (CAPN1), calpain-2 (CAPN2), calpastatin and calmodulin (CaM) in GC and uninvolved gastric mucosa tissues with immunohistochemistry. Results demonstrated that CAPN2 protein level increased in GCs compared with normal tissues, while calpastatin and CaM protein level decreased. No evident alterations were observed for CAPN1. Although the protein expression of all these four proteins was not in association with the clinical variables of GC in the present study, higher calpain enzyme activity could be a negative prognostic marker, since calpains are responsible for the generation of active forms of certain proteins that facilitate the progression of cancer. The ratio of (CAPN1 x CAPN2)/(calpastatin x CaM) may serve as a potential index for diagnosis of GC.

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Calpains and cancer: Friends or enemies?

Cited by 62 publications

References 211 publications

Elevated Expression of Calpain-4 Predicts Poor Prognosis in Patients with Gastric Cancer after Gastrectomy

Elevated Expression of Calpain-4 Predicts Poor Prognosis in Patients with Gastric Cancer after Gastrectomy

GAS2–Calpain2 axis contributes to the growth of leukemic cells

Comparison of the protein expression of calpain-1, calpain-2, calpastatin and calmodulin between gastric cancer and normal gastric mucosa

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Calpains and cancer: Friends or enemies?

Cited by 62 publications

References 211 publications

Elevated Expression of Calpain-4 Predicts Poor Prognosis in Patients with Gastric Cancer after Gastrectomy

Elevated Expression of Calpain-4 Predicts Poor Prognosis in Patients with Gastric Cancer after Gastrectomy

GAS2&ndash;Calpain2 axis contributes to the growth of leukemic cells

Comparison of the protein expression of calpain-1, calpain-2, calpastatin and calmodulin between gastric cancer and normal gastric mucosa

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GAS2–Calpain2 axis contributes to the growth of leukemic cells