SMARCA4/2 loss inhibits chemotherapy-induced apoptosis by restricting IP3R3-mediated Ca2+ flux to mitochondria

Xue, Yibo; Morris, James B.; Yang, Kangning; Fu, Zheng Qing; Zhu, Xianbing; Johnson, Fraser; Meehan, Brian; Witkowski, Leora; Yasmeen, Amber; Golenár, Tünde; Coatham, Mackenzie; Morin, Geneviève; Monast, Anie; Pilon, Virginie; Fiset, Pierre; Jung, Sungmi; Gonzalez, Anne V.; Camilleri-Broët, Sophie; Fu, Lili; Postovit, Lynne-Marie; Spicer, Jonathan; Gotlieb, Walter H.; Guiot, Marie‐Christine; Rak, Janusz; Park, Morag; Lockwood, William W.; Foulkes, William D.; Prudent, Julien; Huang, Sidong

doi:10.1038/s41467-021-25260-9

Cited by 35 publications

(29 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BRCA1-associated protein 1 (BAP1) [74] and BCL-2-related ovarian killer (BOK) [75] have also been found to stabilize IP3R, leading to increased apoptosis sensitivity. Moreover, SMARCA4/2 [36] elicits similar outcome by promoting IP3R transcription. Together, these findings point to a view that Ca 2+ homeostasis dysregulation is widely involved in tumor-driven events, providing potential new therapeutic directions for tumor therapy (Figure 3).…”

Section: Trends Trends In In Cell Biologymentioning

confidence: 85%

“…Increased IP3R3 expression or activities [18,35] induces proliferation as well as apoptosis resistance in multiple cancer cells. Paradoxically, IP3R3 elicits proapoptotic effects in ovarian and lung cancer cells, resulting in cisplatin sensibility by enhancing Ca 2+ transfer from the ER to mitochondria [36]. Additionally, anti-and proapoptotic functions of IP3Rs have been assigned to IP3R3 and IP3R1, respectively, in the same cancer context [37].…”

Section: Open Accessmentioning

confidence: 99%

See 1 more Smart Citation

Calcium homeostasis and cancer: insights from endoplasmic reticulum-centered organelle communications

Zheng¹,

Wang²,

Dong³

et al. 2023

Trends in Cell Biology

103

View full text Add to dashboard Cite

Section: Trends Trends In In Cell Biologymentioning

confidence: 85%

Section: Open Accessmentioning

confidence: 99%

Calcium homeostasis and cancer: insights from endoplasmic reticulum-centered organelle communications

Zheng¹,

Wang²,

Dong³

et al. 2023

Trends in Cell Biology

103

View full text Add to dashboard Cite

“…ARID1A and ARID1B encode members of the SWI/SNF (SWItch/Sucrose Non-Fermentable) ATP-dependent chromatin remodeling complex important for interaction of this complex with DNA, both genes being mutated in OCCC and endometrioid ovarian cancers ( McCluggage and Stewart, 2021 ). The SWI/SNF complex is also disrupted in the very rare SCCOHT with mutation of SMARCA4 and epigenetic silencing of SMARCA2 that encode catalytic subunits important for nucleosome sliding and eviction ( Jelinic et al, 2016 ; Xue et al, 2021 ). OCCC and endometrioid carcinomas also have in common a disrupted PTEN-PI3K pathway with mutations observed in PTEN and PIK3CA , as well as mutations in CTNNB1 ( Kuo et al, 2009 ; Hollis et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Modelling of Ovarian Cancer: From Cell Lines to Organoids for Discovery and Personalized Medicine

Yee

Dickson

Muntasir

et al. 2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Ovarian cancer has the highest mortality of all of the gynecological malignancies. There are several distinct histotypes of this malignancy characterized by specific molecular events and clinical behavior. These histotypes have differing responses to platinum-based drugs that have been the mainstay of therapy for ovarian cancer for decades. For histotypes that initially respond to a chemotherapeutic regime of carboplatin and paclitaxel such as high-grade serous ovarian cancer, the development of chemoresistance is common and underpins incurable disease. Recent discoveries have led to the clinical use of PARP (poly ADP ribose polymerase) inhibitors for ovarian cancers defective in homologous recombination repair, as well as the anti-angiogenic bevacizumab. While predictive molecular testing involving identification of a genomic scar and/or the presence of germline or somatic BRCA1 or BRCA2 mutation are in clinical use to inform the likely success of a PARP inhibitor, no similar tests are available to identify women likely to respond to bevacizumab. Functional tests to predict patient response to any drug are, in fact, essentially absent from clinical care. New drugs are needed to treat ovarian cancer. In this review, we discuss applications to address the currently unmet need of developing physiologically relevant in vitro and ex vivo models of ovarian cancer for fundamental discovery science, and personalized medicine approaches. Traditional two-dimensional (2D) in vitro cell culture of ovarian cancer lacks critical cell-to-cell interactions afforded by culture in three-dimensions. Additionally, modelling interactions with the tumor microenvironment, including the surface of organs in the peritoneal cavity that support metastatic growth of ovarian cancer, will improve the power of these models. Being able to reliably grow primary tumoroid cultures of ovarian cancer will improve the ability to recapitulate tumor heterogeneity. Three-dimensional (3D) modelling systems, from cell lines to organoid or tumoroid cultures, represent enhanced starting points from which improved translational outcomes for women with ovarian cancer will emerge.

show abstract

“…All three complexes contain an ATPase subunit, either SMARCA4 (also known as BRG1) or SMARCA2 (also known as BRM). These ATPase subunits, which are collectively known as Swi2/Snf2 bromodomains, together with SMARCB1 (also known as INI1), SMARCC1 (also known as BAF155), and SMARCC2 (also known as BAF170), constitute the core of the canonical BAF chromatin remodelling complexes 4,5 .…”

Section: Introductionmentioning

confidence: 99%

Switch/sucrose‐non‐fermentable (SWI/SNF) complex (SMARCA4, SMARCA2, INI1/SMARCB1)‐deficient colorectal carcinomas are strongly associated with microsatellite instability: an incidence study in 4508 colorectal carcinomas

et al. 2022

View full text Add to dashboard Cite

Aims Loss of expression of mammalian switch/sucrose‐non‐fermentable (SWI/SNF) [BRG1/BRM‐associated factor (BAF)] complex subunits, including SMARCA4, SMARCA2 and INI1/SMARCB1 (termed SWI/SNF complex deficiency), has been reported in colorectal carcinomas (CRCs) but its frequency and clinical significance are uncertain. Methods and results We performed immunohistochemistry for SMARCA4, SMARCA2 and SMARCB1 on 4508 consecutive resected CRCs. Loss of SMARCA4 expression was found in 13 cases (0.3%), loss of SMARCA2 expression was found in 59 cases (1.3%), and loss of SMARCB1 expression was found in 21 cases (0.4%). Some CRCs showed loss of expression of more than one subunit, so that 84 CRCs (1.7%) were deficient for at least one component. SWI/SNF complex deficiency was associated with higher grade, a right‐sided location, mismatch repair deficiency, and BRAF V600E mutation (P < 0.05); 5.8% of mismatch repair‐deficient (MMRd) cases and 5.4% of BRAF V600E‐mutant cases were SWI/SNF complex‐deficient, as compared with 0.9% and 0.4% of mismatch repair‐proficient and BRAF‐wild‐type cases (P < 0.001). Any loss of SMARCB1 expression and global loss of SMARCA2 expression were associated with statistically significant worse overall survival, whereas SMARCA4‐deficient cases showed a trend only towards poor overall survival (P = 0.121). In multivariate analysis, any loss of SMARCA4 expression and global loss of SMARCA2 expression were associated with worse survival [odds ratio (OR) 3.33, P = 0.019; and OR 3.39, P < 0.001]. Of particular note, among the subgroup of cases that were MMRd and BRAF V600E‐mutated (otherwise considered to be a good prognostic group), loss of SMARCA4 expression was associated with much worse median survival (10.5 months versus 110.9 months; P = 0.003). Conclusions SWI/SNF complex deficiency is rare in CRC but is enriched in MMRd cases. Identifying these cases has morphological associations and prognostic significance, and in the future may have potential therapeutic implications.

show abstract

SMARCA4/2 loss inhibits chemotherapy-induced apoptosis by restricting IP3R3-mediated Ca2+ flux to mitochondria

Cited by 35 publications

References 93 publications

Calcium homeostasis and cancer: insights from endoplasmic reticulum-centered organelle communications

Calcium homeostasis and cancer: insights from endoplasmic reticulum-centered organelle communications

Three-Dimensional Modelling of Ovarian Cancer: From Cell Lines to Organoids for Discovery and Personalized Medicine

Switch/sucrose‐non‐fermentable (SWI/SNF) complex (SMARCA4, SMARCA2, INI1/SMARCB1)‐deficient colorectal carcinomas are strongly associated with microsatellite instability: an incidence study in 4508 colorectal carcinomas

Contact Info

Product

Resources

About