Unfolded protein response activated by endoplasmic reticulum stress in pancreatic cancer: potential therapeutical target

Long, Di; Chen, Kai; Yang, Yinmo; Tian, Xiaodong

doi:10.52586/5061

Cited by 4 publications

(4 citation statements)

References 61 publications

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“…Additionally, both RIP1 and RIP2 downregulated pathways were involved in cancer progression, and this finding was consistent with the SRP9 immunohistochemistry results, in which the nuclear staining >50% group had significantly better RFS than the nuclear staining ≤50% group. Consistent with the GSEA analysis, c-Myc ( 32 ), E2F-1 ( 33 ), G2M checkpoint ( 34 ), oxidative phosphorylation ( 35 ), unfolded protein response ( 36 ) and KRAS mutation ( 37 ) have been reported to be associated with pathways in pancreatic cancer development.…”

Section: Discussionsupporting

confidence: 66%

Significance of signal recognition particle 9 nuclear translocation: Implications for pancreatic cancer prognosis and functionality

Sato,

Meng,

Sasaki

et al. 2024

Int J Oncol

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Signal recognition particles (SRPs) are essential for regulating intracellular protein transport and secretion. Patients with tumors with high SRP9 expression tend to have a poorer overall survival. However, to the best of our knowledge, no reports have described the relationship between SRP9 localization and prognosis in pancreatic cancer. Thus, the present study aimed to investigate this relationship. Immunohistochemical staining for SRP9 using excised specimens from pancreatic cancer surgery cases without preoperative chemotherapy or radiotherapy showed that SRP9 was preferentially expressed in the nucleus of the cancerous regions in some cases, which was hardly detected in other cases, indicating that SRP9 was transported to the nucleus in the former cases. To compare the prognosis of patients with SRP9 nuclear translocation, patients were divided into two groups: Those with a nuclear translocation rate of >50% and those with a nuclear translocation rate of ≤50%. The nuclear translocation rate of >50% group had a significantly better recurrence-free survival than the nuclear translocation rate of ≤50% group (P=0.037). Subsequent in vitro experiments were conducted; notably, the nuclear translocation rate of SRP9 was reduced under amino acid-deficient conditions, suggesting that multiple factors are involved in this phenomenon. To further study the function of SRP9 nuclear translocation, in vitro experiments were performed by introducing SRP9 splicing variants (v1 and v2) and their deletion mutants lacking C-terminal regions into MiaPaCa pancreatic cancer cells. The results demonstrated that both splicing variants showed nuclear translocation regardless of the C-terminal deletions, suggesting the role of the N-terminal regions. Given that SRP9 is an RNA-binding protein, the study of RNA immunoprecipitation revealed that signaling pathways involved in cancer progression and protein translation were downregulated in nuclear-translocated v1 and v2. Undoubtedly, further studies of the nuclear translocation of SRP9 will open an avenue to optimize the precise evaluation and therapeutic control of pancreatic cancer.

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Section: Discussionsupporting

confidence: 66%

Significance of signal recognition particle 9 nuclear translocation: Implications for pancreatic cancer prognosis and functionality

Sato,

Meng,

Sasaki

et al. 2024

Int J Oncol

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“…Additionally, OA can destroy the homeostasis of the endoplasmic reticulum (ER), but it can be rebuilt by the unfolded protein response (UPR), which is mainly mediated by protein kinase RNA-like ER kinase (PERK), inositol-requiring enzyme 1α (IRE-1α) and activating transcription factor 6 (ATF6) ( Figure 5 ) [ 125 ‒ 127 ] . Among these pathways, both PERK and IRE-1α can regulate actin cytoskeleton dynamics through the binding with filamin A, and filamin A regulates the action of actin filaments and cytoskeleton dynamics, facilitating cell migration [128] .…”

Section: The Mechanism Of Mgf In Chondrocytes and Cartilage Defectsmentioning

confidence: 99%

The role of mechano growth factor in chondrocytes and cartilage defects: a concise review

Liu¹,

Duan²,

Zhang³

et al. 2023

ABBS

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Mechano growth factor (MGF), an isoform of insulin-like growth factor 1 (IGF-1), is recognized as a typical mechanically sensitive growth factor and has been shown to play an indispensable role in the skeletal system. In the joint cavity, MGF is highly expressed in chondrocytes, especially in the damaged cartilage tissue caused by trauma or degenerative diseases such as osteoarthritis (OA). Cartilage is an extremely important component of joints because it functions as a shock absorber and load distributer at the weight-bearing interfaces in the joint cavity, but it can hardly be repaired once injured due to its lack of blood vessels, lymphatic vessels, and nerves. MGF has been proven to play an important role in chondrocyte behaviors, including cell proliferation, migration, differentiation, inflammatory reactions and apoptosis, in and around the injury site. Moreover, under the normalized mechanical microenvironment in the joint cavity, MGF can sense and respond to mechanical stimuli, regulate chondrocyte activity, and maintain the homeostasis of cartilage tissue. Recent reports continue to explain its effects on various cell types and sport-related tissues, but its role in cartilage development, homeostasis and disease occurrence is still controversial, and its internal biological mechanism is still elusive. In this review, we summarize recent discoveries on the role of MGF in chondrocytes and cartilage defects, including tissue repair at the macroscopic level and chondrocyte activities at the microcosmic level, and discuss the current state of research and potential gaps in knowledge.

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“…In different types of tumors, various oncogenic factors and transcriptional and metabolic abnormalities act synergistically to bring tumor cells into a sustained state of ERS. Activation of ERS and its downstream signaling pathways coordinate a dynamic balance of proteins that becomes a key factor in tumor growth, angiogenesis, resistance to radiotherapy, and response to immunotherapy 9–11 . When misfolded or unfolded proteins exceed the capacity of ER processing, it leads to ERS and stimulates unfolded protein response (UPR).…”

Section: Introductionmentioning

confidence: 99%

“…Activation of ERS and its downstream signaling pathways coordinate a dynamic balance of proteins that becomes a key factor in tumor growth, angiogenesis, resistance to radiotherapy, and response to immunotherapy. 9 , 10 , 11 When misfolded or unfolded proteins exceed the capacity of ER processing, it leads to ERS and stimulates unfolded protein response (UPR). UPR is mainly composed of three key pathways: IRE1α, PERK, and ATF6, which jointly regulate the stress response of cells.…”

Section: Introductionmentioning

confidence: 99%

Characteristics of endoplasmic reticulum stress in colorectal cancer for predicting prognosis and developing treatment options

Geng

Xie

et al. 2023

Cancer Medicine

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Background An increasing body of evidence supports an essential role for endoplasmic reticulum stress (ERS) in colorectal cancer (CRC). In this study, we developed an ERS‐related genes (ERSRGs) model to aid in the prognostic evaluation and treatment of CRC patients. Methods The training set and validation set data were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. ERSRGs were obtained from the GeneCards database. A prognostic risk scoring model was constructed using the least absolute shrinkage and selection operator (LASSO) along with univariate Cox regression analysis. To further predict the probability of survival for patients at 1, 2, and 3 years, a nomogram was devised. The advantages of the prognostic risk score model in screening patients’ sensitive to chemotherapy and immunotherapy were analyzed by drug sensitivity analysis and immune correlation analysis. Finally, hub genes associated with poor prognosis in the risk model were screened by Protein–protein interaction (PPI) network and their expression was validated using clinical specimens. Results A risk model for overall survival (OS) was developed using 16 ERSRGs associated with prognosis. Through analyses, we demonstrated a high degree of reliability for the prognostic risk scoring model. The constructed nomograms performed well in predicting patient survival over 1, 3, and 5 years. The calibration curve and decision curve analysis (DCA) supported a high degree of accuracy for the model. Patients in the low‐risk group had a lower IC50 for the common chemotherapy drug, 5‐FU, and responded better to immunotherapy. hub poor prognostic genes were validated in CRC clinical specimens. Conclusion We have identified and validated a new ERS prognostic marker that can accurately predict the survival status of CRC patients for clinicians and better provide personalized treatment plans.

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Unfolded protein response activated by endoplasmic reticulum stress in pancreatic cancer: potential therapeutical target

Cited by 4 publications

References 61 publications

Significance of signal recognition particle 9 nuclear translocation: Implications for pancreatic cancer prognosis and functionality

Significance of signal recognition particle 9 nuclear translocation: Implications for pancreatic cancer prognosis and functionality

The role of mechano growth factor in chondrocytes and cartilage defects: a concise review

Characteristics of endoplasmic reticulum stress in colorectal cancer for predicting prognosis and developing treatment options

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