AlphaB-crystallin and breast cancer: role and possible therapeutic strategies

Caporossi, Daniela; Parisi, Attilio; Fantini, Cristina; Grazioli, Elisa; Cerulli, Claudia; Dimauro, Ivan

doi:10.1007/s12192-020-01175-0

Cited by 13 publications

(11 citation statements)

References 108 publications

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“…A comparison of SNP array data revealed that CRYAB is gained or amplified in many cancers such as B-Cell neoplasms, non-small cell lung cancer, glioblastoma, melanoma, colorectal, bladder, pancreatic, breast, endometrial, renal, thyroid cancer, and sarcoma (Fig S1a and negative correlation with hormone expression (Fig S2a , 2b and 2c). Consistent with this, CRYAB overexpression predominantly occurs in triple-negative breast cancer that lack expression of hormone receptors 7 . Notably, autophagy, angiogenesis and, hypoxia have a significant-positive correlation to CRYAB expression across several cancer types such as adenocarcinomas of colon, lung, prostate, and stomach (Fig S2c ,).…”

Section: Cryab Is Frequently Gained and Overexpression Is Associated ...supporting

confidence: 63%

“…For instance, in breast cancer (n=753) there is a positive correlation between CRYABexpression and Ras/MAPK (r=0.1863, p=2.6 x 10−07); PI3K/Akt (r=0.1904, p=1.4 x 10−07); epithelial-mesenchymal transition (EMT) score (r=0.2750 , p=1.6 x 10−14) ; apoptosis (r=0.1238, p=0.0007); autophagy (r=0.1492, p=6.3 x 10−07 ); angiogenesis ( r=0.3059, p=6.8 x 10−25 ); and hypoxia based on Elvidge et al (r=0.5320, p=1.2 x 10−79)Oncogene and negative correlation with hormone expression (Fig S2a, 2b and 2c). Consistent with this, CRYAB overexpression predominantly occurs in triple-negative breast cancer that lack expression of hormone receptors7 . Notably, autophagy, angiogenesis and, hypoxia have a significant-positive correlation to CRYAB expression across several cancer types such as adenocarcinomas of colon, lung, prostate, and stomach (FigS2c,).…”

supporting

confidence: 66%

“…In clear cell and papillary type renal cell carcinoma and colorectal cancer, CRYAB is used as a marker for higher tumor stage and distant metastases, and in osteosarcoma, it is a marker for increased metastases and poor chemotherapy response 6 . In breast cancer, CRYAB is a marker for aggressive behavior in triple-negative basal-like breast cancer and mammary metaplastic carcinoma and its overexpression is associated with the presence of lymph nodal and brain metastasis and relapse 7 . CRYAB is also categorized as a marker for lower overall survival in cancers such as renal cell carcinoma, osteosarcoma, colorectal, hepatocellular carcinoma, gastric, ovarian, and non-small cell lung cancer 6 .…”

Section: Introductionmentioning

confidence: 99%

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Alpha-B-Crystallin overexpression is sufficient to promote tumorigenesis and metastasis in mice

Rashidieh

Bain

Tria

et al. 2022

Preprint

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αB-Crystallin is a heat shock chaperone protein which binds to misfolded proteins to prevent their aggregation. It is overexpressed in a wide-variety of cancers. Previous studies using human cancer cell lines and human xenograft models have reported tumor suppressor or tumor promoter (oncogene) roles for αB-Crystallin depending on cellular context and environmental conditions. To determine the causal relationship between CRYAB overexpression and cancer, we generated a Cryab overexpression knock-in mouse model. This model revealed that constitutive overexpression of Cryab results in the formation of a variety of lethal spontaneous primary and metastatic tumors in mice. In vivo, the overexpression of Cryab correlated with the upregulation of epithelial-to-mesenchymal (EMT) markers, angiogenesis and some oncogenic proteins including Basigin. In vitro, using E1A/Ras transformed mouse embryonic fibroblasts (MEFs), we observed that the overexpression of Cryab led to the promotion of cell survival via upregulation of Akt signaling and downregulation of pro-apoptotic pathway mediator JNK, with subsequent attenuation of apoptosis as assessed by cleaved caspase-3. Overall, through the generation and characterization of Cryab overexpression model, we provide evidence supporting the role of αB-Crystallin as an oncogene, where its upregulation is sufficient to induce tumors, promote cell survival and inhibit apoptosis.

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Section: Cryab Is Frequently Gained and Overexpression Is Associated ...supporting

confidence: 63%

supporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

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Alpha-B-Crystallin overexpression is sufficient to promote tumorigenesis and metastasis in mice

Rashidieh

Bain

Tria

et al. 2022

Preprint

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“…Though in general the phosphorylation has an augmentative effect, it is possible that modulation of the activity upon phosphorylation might depend on the target protein and its interactions [123]. Further details about the phosphorylation of CRYAB in various physiological or pathological conditions can be found elsewhere [107,124].…”

Section: Stress Proteins: αB-crystallinmentioning

confidence: 99%

Function and Fiber-Type Specific Distribution of Hsp60 and αB-Crystallin in Skeletal Muscles: Role of Physical Exercise

D’Amico

Fiore

Caporossi

et al. 2021

Biology

Self Cite

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Skeletal muscle is a plastic and complex tissue, rich in proteins that are subject to continuous rearrangements. Skeletal muscle homeostasis can be affected by different types of stresses, including physical activity, a physiological stressor able to stimulate a robust increase in different heat shock proteins (HSPs). The modulation of these proteins appears to be fundamental in facilitating the cellular remodeling processes related to the phenomenon of training adaptations such as hypertrophy, increased oxidative capacity, and mitochondrial activity. Among the HSPs, a special attention needs to be devoted to Hsp60 and αB-crystallin (CRYAB), proteins constitutively expressed in the skeletal muscle, where their specific features could be highly relevant in understanding the impact of different volumes of training regimes on myofiber types and in explaining the complex picture of exercise-induced mechanical strain and damaging conditions on fiber population. This knowledge could lead to a better personalization of training protocols with an optimal non-harmful workload in populations of individuals with different needs and healthy status. Here, we introduce for the first time to the reader these peculiar HSPs from the perspective of exercise response, highlighting the control of their expression, biological function, and specific distribution within skeletal muscle fiber-types.

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“…AlphaB-crystallin (CRYAB, HSPB5) and HSP27 are both members of the small heat shock protein family (Kappé et al 2010) and each are implicated in the progression of breast cancer (Caporossi et al 2021;Choi et al 2019;Wang et al 2020). Both sHSPs are considered potential targets for the treatment of breast cancer (Caporossi et al 2021;Lang et al 2019;Wang et al 2020). Their individual contributions to the breast cancer chaperome and epichaperome networks have been investigated (Rodina et al 2016;Wang et al 2019;Yan et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Cluster analyses of the TCGA and a TMA dataset using the coexpression of HSP27 and CRYAB improves alignment with clinical-pathological parameters of breast cancer and suggests different epichaperome influences for each sHSP

Quinlan

Figeuredo

Mongan

et al. 2022

Cell Stress and Chaperones

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Our cluster analysis of the Cancer Genome Atlas for co-expression of HSP27 and CRYAB in breast cancer patients identified three patient groups based on their expression level combination (high HSP27 + low CRYAB; low HSP27 + high CRYAB; similar HSP27 + CRYAB). Our analyses also suggest that there is a statistically significant inverse relationship between HSP27 and CRYAB and known clinicopathological markers in breast cancer. Screening an unbiased 248 breast cancer patient tissue microarray (TMA) for the protein expression of HSP27 and phosphorylated HSP27 (HSP27-82pS) with CRYAB also identified three patient groups based on HSP27 and CRYAB expression levels. TMA24 also had recorded clinical-pathological parameters, such as ER and PR receptor status, patient survival, and TP53 mutation status. High HSP27 protein levels were significant with ER and PR expression. HSP27-82pS associated with the best patient survival (Log Rank test). High CRYAB expression in combination with wild-type TP53 was significant for patient survival, but a different patient outcome was observed when mutant TP53 was combined with high CRYAB expression. Our data suggest that HSP27 and CRYAB have different epichaperome influences in breast cancer, but more importantly evidence the value of a cluster analysis that considers their coexpression. Our approach can deliver convergence for archival datasets as well as those from recent treatment and patient cohorts and can align HSP27 and CRYAB expression to important clinical-pathological features of breast cancer.

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AlphaB-crystallin and breast cancer: role and possible therapeutic strategies

Cited by 13 publications

References 108 publications

Alpha-B-Crystallin overexpression is sufficient to promote tumorigenesis and metastasis in mice

Alpha-B-Crystallin overexpression is sufficient to promote tumorigenesis and metastasis in mice

Function and Fiber-Type Specific Distribution of Hsp60 and αB-Crystallin in Skeletal Muscles: Role of Physical Exercise

Cluster analyses of the TCGA and a TMA dataset using the coexpression of HSP27 and CRYAB improves alignment with clinical-pathological parameters of breast cancer and suggests different epichaperome influences for each sHSP

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