Stress-induced phosphoprotein 1 promotes pancreatic cancer progression through activation of the FAK/AKT/MMP signaling axis

Ye, Jing; Liang, Wenqing; Liu, Jian; Zhang, Lin; Wei, Jianguo; Zhu, Yafang; Yang, Jianhui; Ji, Kewei; Huang, Zhenpeng

doi:10.1016/j.prp.2019.152564

Cited by 20 publications

(24 citation statements)

References 24 publications

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“…As a KRAS mutated cell line, survival mechanisms are upregulated per se in Panc1 cells involving elevated Akt expression and activation [ 53 ]. In line with earlier studies by other groups, we also confirmed relatively high activated p-Akt/Ser473 levels in Panc1 cells using flow cytometry [ 54 , 55 ]. This showed a trend of downregulation both after mEHT monotherapy, and when mEHT was combined with radiotherapy.…”

Section: Discussionsupporting

confidence: 92%

Modulated Electro-Hyperthermia Resolves Radioresistance of Panc1 Pancreas Adenocarcinoma and Promotes DNA Damage and Apoptosis In Vitro

Forika

Balogh

Vancsik

et al. 2020

IJMS

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The poor outcome of pancreas ductal adenocarcinomas (PDAC) is frequently linked to therapy resistance. Modulated electro-hyperthermia (mEHT) generated by 13.56 MHz capacitive radiofrequency can induce direct tumor damage and promote chemo- and radiotherapy. Here, we tested the effect of mEHT either alone or in combination with radiotherapy using an in vivo model of Panc1, a KRAS and TP53 mutant, radioresistant PDAC cell line. A single mEHT shot of 60 min induced ~50% loss of viable cells and morphological signs of apoptosis including chromatin condensation, nuclear shrinkage and apoptotic bodies. Most mEHT treatment related effects exceeded those of radiotherapy, and these were further amplified after combining the two modalities. Treatment related apoptosis was confirmed by a significantly elevated number of annexin V single-positive and cleaved/activated caspase-3 positive tumor cells, as well as sub-G1-phase tumor cell fractions. mEHT and mEHT+radioterapy caused the moderate accumulation of γH2AX positive nuclear foci, indicating DNA double-strand breaks and upregulation of the cyclin dependent kinase inhibitor p21waf1 besides the downregulation of Akt signaling. A clonogenic assay revealed that both mono- and combined treatments affected the tumor progenitor/stem cell populations too. In conclusion, mEHT treatment can contribute to tumor growth inhibition and apoptosis induction and resolve radioresistance of Panc1 PDAC cells.

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Section: Discussionsupporting

confidence: 92%

Modulated Electro-Hyperthermia Resolves Radioresistance of Panc1 Pancreas Adenocarcinoma and Promotes DNA Damage and Apoptosis In Vitro

Forika

Balogh

Vancsik

et al. 2020

IJMS

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“…Andreasi et al also reported that plasma vasostatin-1 concentrations could be used to preoperatively predict the presence of MVI [ 65 ]. Other studies have revealed that MVI is positively correlated with STIP-1 and CD34 levels in PDAC [ 11 , 14 ]. Further research may help develop a model to predict the risk of MVI based on non-invasive parameters, similar to models for liver cancer, which will require studies to assess the relationships between MVI, radiographic parameters, and clinical parameters in PDAC cases.…”

Section: Discussionmentioning

confidence: 99%

“…In the studies that clearly explained the definition of microvascular or lymphatic invasion, 4 defined MVI as originating from blood vessels [ 9 , 10 , 14 , 32 ], 1 defined LVI as originating from lymphatic vessels [ 32 ], and 1 did not distinguish between them [ 17 ]. Although other studies specifically used the terms MVI or LVI, all of these studies’ research objectives were regarding MVI according to the articles’ descriptions [ 7 , 8 , 11 , 12 , 15 , 20 – 24 , 28 , 29 ]. In addition, from the data in Figure 3 , we found that although different studies have different definitions of MVI, there was no significant difference between the 2 groups (MVI vs LVI) in either DFS or OS.…”

Section: Discussionmentioning

confidence: 99%

“…Even though EMT is an important step in PDAC metastasis [ 38 – 41 ], the direct relationship between EMT and MVI in PDAC has rarely been reported in the literature. Stress-inducible phosphoprotein-1 (STIP1) is positively correlated with MVI in PDAC [ 11 ] and induces EMT in gastric and lung cancers [ 42 , 43 ], and it may be the potential key link between EMT and MVI in PDAC.…”

Section: Discussionmentioning

confidence: 99%

“…MVI mostly describes microvessel invasion [ 18 ], while LVI is used to indicate micro-lymph-tubule invasion [ 19 ]. However, in the literature reviewed, only a few studies distinguished the 2 terms [ 9 , 15 ]; in most cases, they refer to the same pathological characteristics [ 7 , 11 , 12 , 14 , 20 – 23 ], which leads to confusion. In addition, the incidence of MVI in PDAC varies considerably [ 7 – 12 , 14 , 15 , 20 – 24 ] and the literature rarely discusses the potential mechanism of MVI in the progression of PDAC, so the mechanism and clinical significance of MVI in poor PDAC outcomes remains incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Prognostic Significance of Microvascular Invasion in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis

Pan

Liu

et al. 2021

Med Sci Monit

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Background The incidence, pathogenesis, and prognostic effect of microvascular invasion on pancreatic ductal adenocarcinoma (PDAC) remain controversial. This study aimed to summarize the incidence, pathogenesis, role in clinical management, recurrence, and prognostic significance of microvascular invasion in PDAC. Material/Methods A literature review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Systematic literature searches were conducted using PubMed and Google Scholar up to February 2021. Results Seventeen studies were included in the meta-analysis. The incidence of microvascular invasion was 49.0% (95% confidence interval [CI], 43.8–54.5%) among PDAC patients who underwent surgery. The weighted multivariate Cox proportional hazards model hazard ratio for disease-free survival of 8 studies was 1.78 (95% CI 1.53–2.08, P<0.001), and there was no statistically significant difference between the subgroups (P=0.477). The hazard ratio for overall survival of 14 studies was 1.49 (95% CI 1.27–1.74, P<0.001), and there was no statistically significant difference between the subgroups (P=0.676). Conclusions Microvascular invasion occurred in nearly half of PDAC patients after surgery and was closely related to disease-free and overall survival. Understanding the role of microvascular invasion in PDAC will help provide more personalized and effective preoperative or postoperative strategies to achieve better survival outcomes.

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The Role of ECM Remodeling, EMT, and Adhesion Molecules in Cancerous Neural Invasion: Changing Perspectives

Mukherjee

Wai

et al. 2022

Advanced Biology

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the nerve, is often used synonymously with the term PNI. It is important to differentiate between these two terms as the former can be determined using imaging techniques as it is apparent both clinically and radiologically whereas the latter is more of a histological diagnosis. [4,5] The presence of PNI in malignant neoplasms serves as a marker for poor clinical prognosis and higher mortality rate among patients. PNI is most commonly detected in the aggressive pancreatic, prostate, head and neck, colorectal and gastric cancers. [6] Importantly, in some of these cancers, PNI is the only method of metastasis and it can exist independently without vascular and lymphatic invasion. [2,7] In head and neck, the prevalence of PNI varies between 25-80% when compared to non-PNI cases, whereas in pancreatic cancer, 90% of patients exhibit PNI. [8,9] Furthermore, multiple population-based studies carried out over the years have reported no significant difference in the development of PNI based on age, gender, ethnicity/race or other demographic risk factors like smoking history. [10,11,12] Knowledge of the structure and composition of the nerve and its perineural niche is integral to understanding PNI. The peripheral nerves are primarily composed of Schwann cells, fibroblasts, blood vessels along with axon bundles. The Schwann cells are essential for the maintenance of the axons as well as for the production of myelin in the peripheral nervous system. [13] The innermost endoneurium is composed of the extracellular matrix (ECM), fibroblasts and collagen. It is a delicate layer of connective tissue which wraps around the axon and capillaries. The axons are supported and protected by endoneurial cells which are found in this layer. [14] The perineurium has one or more layers of flat epithelial-like cells which group the axons and endoneurium into fascicles. The presence of tight and adherens junctions (AJs) in the epithelial layer adds to the robustness of this layer thereby providing a permeable, but selective barrier between the surrounding axons and tissues. [15] And finally, the outermost epineurium consists of a dense connective tissue layer composed of elastin fibers and collagen which surround the entire nerve bundle. [16] Numerous blood vessels can also be found in this layer as they serve as the vascular supply to the nerve. Based on the structure of the nerve, Leibig et al. [17] combined past and present definitions and defined PNI as the presence of cancer cells along the nerves Perineural invasion (PNI) refers to the cancerous invasion of nerves. It provides an alternative route for metastatic invasion and can exist independently in the absence of lymphatic or vascular invasion.It is a prominent characteristic of specific aggressive malignancies where it correlates with poor prognosis. The clinical significance of PNI is widely recognized despite a lack of understanding of the molecular mechanisms underlying its pathogenesis. The interaction between the nerve and the cancer cells is the most pivotal PNI step which...

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Stress-induced phosphoprotein 1 promotes pancreatic cancer progression through activation of the FAK/AKT/MMP signaling axis

Cited by 20 publications

References 24 publications

Modulated Electro-Hyperthermia Resolves Radioresistance of Panc1 Pancreas Adenocarcinoma and Promotes DNA Damage and Apoptosis In Vitro

Modulated Electro-Hyperthermia Resolves Radioresistance of Panc1 Pancreas Adenocarcinoma and Promotes DNA Damage and Apoptosis In Vitro

Prognostic Significance of Microvascular Invasion in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis

The Role of ECM Remodeling, EMT, and Adhesion Molecules in Cancerous Neural Invasion: Changing Perspectives

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