Roles of the nervous system in pancreatic cancer

Wakiya, Taiichi; Ishido, Keinosuke; Yoshizawa, Tadashi; Kanda, Taishu; Hakamada, Kenichi

doi:10.1002/ags3.12459

Cited by 14 publications

(14 citation statements)

References 142 publications

(342 reference statements)

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“…Adenoma, cystadenoma, lipoma, fibroma, hemangioma, lymphangioma, and neuroma are benign non-endocrine pancreas tumors [ 9 ]. Moreover, scientific data revealed that the nervous system is involved in PC carcinogenesis [ 12 ], so pancreatic tumors can be neuroendocrine neoplasms [ 13 ]. Therefore, pancreatic neuroendocrine tumors or PNETs develop from the endocrine component of the pancreas [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects

Stanciu¹,

Ioniţă-Radu²,

Ştefani³

et al. 2022

IJMS

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Although pancreatic cancer (PC) was considered in the past an orphan cancer type due to its low incidence, it may become in the future one of the leading causes of cancer death. Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of PC, being a highly aggressive malignancy and having a 5-year survival rate of less than 10%. Non-modifiable (family history, age, genetic susceptibility) and modifiable (smoking, alcohol, acute and chronic pancreatitis, diabetes mellitus, intestinal microbiota) risk factors are involved in PC pathogenesis. Chronic inflammation induced by various factors plays crucial roles in PC development from initiation to metastasis. In multiple malignant conditions such as PC, cytokines, chemokines, and growth factors activate the class I phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) (PI3K/AKT/mTOR) signaling pathway, which plays key roles in cell growth, survival, proliferation, metabolism, and motility. Currently, mTOR, AKT, and PI3K inhibitors are used in clinical studies. Moreover, PI3K/mTOR dual inhibitors are being tested in vitro and in vivo with promising results for PC patients. The main aim of this review is to present PC incidence, risk factors, tumor microenvironment development, and PI3K/AKT/mTOR dysregulation and inhibitors used in clinical, in vivo, and in vitro studies.

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Section: Introductionmentioning

confidence: 99%

Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects

Stanciu¹,

Ioniţă-Radu²,

Ştefani³

et al. 2022

IJMS

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“…Frequent and diverse somatic aberrations in genes involved in regulating axon guidance have already been demonstrated to be important in pancreatic carcinogenesis ( Biankin et al, 2012 ). This, along with the observation that the number and size of intrapancreatic nerves increase in PDAC, a process called pancreatic cancer–associated neural remodeling (PANR) ( Wakiya et al, 2021 ), underlines the possible importance of sex’s role in PC progression and how male hormones may affect the expression of involved genes. On the other hand, the presence of several TFs among the AER/ERE-containing genes may emphasize a more possible effect of sex on disease progression.…”

Section: Discussionmentioning

confidence: 95%

Gender-related differentially expressed genes in pancreatic cancer: possible culprits or accomplices?

Ramezankhani

Ghavidel²,

Rashidi³

et al. 2022

Front. Genet.

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Pancreatic cancer (PC) is one of the leading causes of cancer mortality worldwide, and its incidence and mortality rate in several regions is higher in male patients. Although numerous efforts have been made to enhance the clinical outcomes of existing therapeutic regimens, their efficiency is still low, and drug resistance usually occurs in many patients. In addition, the exact underlying molecular basis that makes PC slightly more prevalent among males remains unknown. Providing information regarding the possible association between gender and PC tumorigenesis may offer important clues for how certain molecular cross-talks can affect PC initiation and/or progression. In this study, we used several microarray expression data to identify the common up- and downregulated genes within one specific gender, which were also specified to have binding sites for androgen and/or estrogen receptors. Using functional enrichment analysis among the others, for all the gene sets found in this study, we have shed light on the plausible importance of the androgenic effectors in tumorigenesis, such as the androgen-regulated expression of the GLI transcription factor and the potential role of testosterone in the extracellular matrix (ECM)–cell interaction, which are known for their importance in tumorigenesis. Moreover, we demonstrated that the biological process axon guidance was highlighted regarding the upregulated genes in male patients. Overall, identification of gene candidates as the possible link between gender and PC progression or survival rates may help in developing strategies to reduce the incidence of this cancer.

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“…Stroma cells produce neural-related factors, which leads to tumor cell proliferation and survival in the primary site and secondary site 21 . Neural cells and neural-related factors have been increasingly perceived as major modulators of the aggressiveness of this lethal disease 19 , 26 , 39 – 41 . PNI is regulated by the interaction between the nerve microenvironment and neurotrophic molecules from cancer cells 11 , 21 , 42 .…”

Section: Discussionmentioning

confidence: 99%

Eukaryotic initiation factor 2 signaling behind neural invasion linked with lymphatic and vascular invasion in pancreatic cancer

Wakiya

Ishido

Kimura

et al. 2021

Sci Rep

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Perineural invasion (PNI) is a typical poor prognostic factor in pancreatic ductal adenocarcinoma (PDAC). The mechanisms linking PNI to poor prognosis remain unclear. This study aimed to clarify what changes occurred alongside PNI in PDAC. A 128-patient cohort undergoing surgery for early-stage PDAC was evaluated. Subdivided into two groups, according to pathological state, a pancreatic nerve invasion (ne) score of less than three (from none to moderate invasion) was designated as the low-grade ne group. The high-grade (marked invasion) ne group (74 cases, 57.8%) showed a higher incidence of lymphatic metastasis (P = 0.002), a higher incidence of early recurrence (P = 0.004), decreased RFS (P < 0.001), and decreased DSS (P < 0.001). The severity of lymphatic (r = 0.440, P = 0.042) and venous (r = 0.610, P = 0.002) invasions was positively correlated with the ne score. Tumors having abundant stroma often displayed severe ne. Proteomics identified eukaryotic initiation factor 2 (EIF2) signaling as the most significantly enriched pathway in high-grade ne PDAC. Additionally, EIF2 signaling-related ribosome proteins decreased according to severity. Results showed that PNI is linked with lymphatic and vascular invasion in early-stage PDAC. Furthermore, the dysregulation of proteostasis and ribosome biogenesis can yield a difference in PNI severity.

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Roles of the nervous system in pancreatic cancer

Cited by 14 publications

References 142 publications

Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects

Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects

Gender-related differentially expressed genes in pancreatic cancer: possible culprits or accomplices?

Eukaryotic initiation factor 2 signaling behind neural invasion linked with lymphatic and vascular invasion in pancreatic cancer

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