DUSP2 recruits CSNK2A1 to suppress AKT1-mediated apoptosis resistance under hypoxic microenvironment in pancreatic cancer

Zhang, Yangyang; Kong, Rui; Yang, Wenbo; Hu, Keyi; Zhao, Zhongjie; Li, Le; Geng, Xinglong; Liu, Liwei; Chen, Hongze; Liu, Danxi; Luo, Yan; Chen, Hua; Hu, Jisheng; Bei, Sun

doi:10.1016/j.canlet.2023.216288

Cited by 11 publications

(4 citation statements)

References 42 publications

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“…It has been found that FKBP1A is up-regulated in prostate cancer and head and neck squamous cell carcinoma, and enhances paclitaxel-resistance and associates with lymph node metastasis [ 32 , 33 ]. Moreover, Zhang et al reported that DUSP2 promotes apoptosis under hypoxic microenvironment in pancreatic cancer [ 34 ]. Ding at el.…”

Section: Discussionmentioning

confidence: 99%

Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma

Fang,

Li,

Lin

et al. 2024

Cell Death Dis

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Despite that the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved patients’ survival and became the first-line treatment for advanced nasopharyngeal carcinoma (NPC), not all patients could benefit from this therapy. The mechanism underlying the TPF chemoresistance remains unclear. Here, by analyzing gene-expression microarray data and survival of patients who received TPF chemotherapy, we identify transcription factor ATMIN as a chemoresistance gene in response to TPF chemotherapy in NPC. Mass spectrometry and Co-IP assays reveal that USP10 deubiquitinates and stabilizes ATMIN protein, resulting the high-ATMIN expression in NPC. Knockdown of ATMIN suppresses the cell proliferation and facilitates the docetaxel-sensitivity of NPC cells both in vitro and in vivo, while overexpression of ATMIN exerts the opposite effect. Mechanistically, ChIP-seq combined with RNA-seq analysis suggests that ATMIN is associated with the cell death signaling and identifies ten candidate target genes of ATMIN. We further confirm that ATMIN transcriptionally activates the downstream target gene LCK and stabilizes it to facilitate cell proliferation and docetaxel resistance. Taken together, our findings broaden the insight into the molecular mechanism of chemoresistance in NPC, and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.

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Section: Discussionmentioning

confidence: 99%

Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma

Fang,

Li,

Lin

et al. 2024

Cell Death Dis

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Section: Hypoxiamentioning

confidence: 99%

“…The hypoxic state of pancreatic cancer has significant implications for treatment and prognosis. A hypoxic environment can lead to increased malignancy and drug resistance of tumor cells (Sun et al, 2021; H. Wang et al, 2023; Y. Zhang, Kong, et al, 2023). In addition, it can affect the efficacy of radiotherapy and chemotherapy, as these treatment methods typically require oxygen involvement.…”

Section: Characteristics Of Pancreatic Cancermentioning

confidence: 99%

Recent advances in sonodynamic therapy strategies for pancreatic cancer

Cheng,

Ming,

Cao

et al. 2024

WIREs Nanomed Nanobiotechnol

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Pancreatic cancer, a prevalent malignancy of the digestive system, has a poor 5‐year survival rate of around 10%. Although numerous minimally invasive alternative treatments, including photothermal therapy and photodynamic therapy, have shown effectiveness compared with traditional surgical procedures, radiotherapy, and chemotherapy. However, the application of these alternative treatments is constrained by their depth of penetration, making it challenging to treat pancreatic cancer situated deep within the tissue. Sonodynamic therapy (SDT) has emerged as a promising minimally invasive therapy method that is particularly potent against deep‐seated tumors such as pancreatic cancer. However, the unique characteristics of pancreatic cancer, including a dense surrounding matrix, high reductivity, and a hypoxic tumor microenvironment, impede the efficient application of SDT. Thus, to guide the evolution of SDT for pancreatic cancer therapy, this review addresses these challenges, examines current strategies for effective SDT enhancement for pancreatic cancer, and investigates potential future advances to boost clinical applicability.This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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“…TRIM21 inhibits tumor cell apoptosis by promoting ubiquitin-dependent degradation of dual-specificity phosphatase 2 (DUSP2) ( Zhang et al, 2023a ). High expression of glucose-induced degradation-deficient subunit 2 (GID2) is associated with a higher stage and poorer prognosis of PDAC since GID2 inhibits apoptosis by suppressing the ubiquitination of CDKN3 and enhancing its stability ( Deng et al, 2023 ).…”

Section: How E3s and Dubs Influence Various Phenotypes Of Pdacmentioning

confidence: 99%

Ubiquitin signaling in pancreatic ductal adenocarcinoma

Lv,

Zhang,

Peng

et al. 2023

Front. Mol. Biosci.

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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignant tumor of the digestive system, characterized by rapid progression and being prone to metastasis. Few effective treatment options are available for PDAC, and its 5-year survival rate is less than 9%. Many cell biological and signaling events are involved in the development of PDAC, among which protein post-translational modifications (PTMs), such as ubiquitination, play crucial roles. Catalyzed mostly by a three-enzyme cascade, ubiquitination induces changes in protein activity mainly by altering their stability in PDAC. Due to their role in substrate recognition, E3 ubiquitin ligases (E3s) dictate the outcome of the modification. Ubiquitination can be reversed by deubiquitylases (DUBs), which, in return, modified proteins to their native form. Dysregulation of E3s or DUBs that disrupt protein homeostasis is involved in PDAC. Moreover, the ubiquitination system has been exploited to develop therapeutic strategies, such as proteolysis-targeting chimeras (PROTACs). In this review, we summarize recent progress in our understanding of the role of ubiquitination in the development of PDAC and offer perspectives in the design of new therapies against this highly challenging disease.

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DUSP2 recruits CSNK2A1 to suppress AKT1-mediated apoptosis resistance under hypoxic microenvironment in pancreatic cancer

Cited by 11 publications

References 42 publications

Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma

Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma

Recent advances in sonodynamic therapy strategies for pancreatic cancer

Ubiquitin signaling in pancreatic ductal adenocarcinoma

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