2018
DOI: 10.1007/s00280-018-3651-3
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Repression of GRIM19 expression potentiates cisplatin chemoresistance in advanced bladder cancer cells via disrupting ubiquitination-mediated Bcl-xL degradation

Abstract: Disruption of GRIM19/Bcl-xL is a key mechanism of CDDP resistance in advanced BC. Therapeutically, enhancement of GRIM19 expression or employment of p38/JNK inhibitors may serve as resensitizing therapies for subgroups of CDDP-resistant or refractory BC patients.

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Cited by 9 publications
(4 citation statements)
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“…Therefore, cIAP2 might be a promising target for improving chemoradiation strategy in bladder cancer. Suppression of GRIM19 expression impaired ubiquitination-mediated degradation of Bcl-xL in bladder cancer cells, conferring to promotion of cisplatin chemoresistance (85). Overexpression of GRIM19 potentiated cisplatin sensitivity and reduced the invasion and proliferation of bladder cancer cells, which was due to attenuation of Bcl-xL polyubiquitination and degradation (85).…”
Section: Other Deubiquitinases and E3 Ubiquitin Ligasesmentioning
confidence: 99%
“…Therefore, cIAP2 might be a promising target for improving chemoradiation strategy in bladder cancer. Suppression of GRIM19 expression impaired ubiquitination-mediated degradation of Bcl-xL in bladder cancer cells, conferring to promotion of cisplatin chemoresistance (85). Overexpression of GRIM19 potentiated cisplatin sensitivity and reduced the invasion and proliferation of bladder cancer cells, which was due to attenuation of Bcl-xL polyubiquitination and degradation (85).…”
Section: Other Deubiquitinases and E3 Ubiquitin Ligasesmentioning
confidence: 99%
“…The function of BCL-xL is regulated by several kinases, including PLK3 [34], JNK [35], CDK2 [36], and MST1 [37]. Deamidation [38] or ubiquitination [39] of BCL-xL are regulated processes that target it for degradation, and can determine susceptibility to DNA-damaging agents and other death stimuli.…”
Section: Bcl-xl Protein Structurementioning
confidence: 99%
“…BCL-xL protein levels can be detected in low-medium score in a few tissues, including bone marrow, lymph node, brain, and cells in tubules (Figure 2). Deamidation [38] or ubiquitination [39] of BCL-xL are regulated processes that target it for degradation, and can determine susceptibility to DNA-damaging agents and other death stimuli.…”
Section: Bcl-xl Protein Localizationmentioning
confidence: 99%
“…More than 7 in 10 bladder cancers are non-muscle-invasive bladder cancer (NMIBC), which can be treated via immunotherapy and chemotherapy or by surgical resection. However, up to 80% of NMIBC patients have recurrence within 2 years, and around 30% of these patients progress to advanced bladder cancer, with high aggressiveness and mortality [2]. At present, cisplatin- or gemcitabine-based neoadjuvant chemotherapy before radical cystectomy is used for treating advanced bladder cancer [3].…”
Section: Introductionmentioning
confidence: 99%