Oxytocin and oxytocin receptor alterations, decreased survival, and increased chemoresistance in patients with pancreatic cancer

Harricharran, Trisheena; Ogunwobi, Olorunseun O.

doi:10.1016/j.hbpd.2019.12.002

Cited by 5 publications

(3 citation statements)

References 45 publications

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“…Hypothalamic OXT-producing neurons was also found to suppress colitis-associated colorectal cancer 22 . However, OXT/OXTR signaling had been demonstrated to be pro-tumorigenic in lung cancer 23 , melanoma 24 , prostate cancer 54 , and pancreatic cancer 55 . Our findings provide additional mechanistic insights into the pro-metastasis role of OXTR in OSCC development.…”

Section: Discussionmentioning

confidence: 99%

OXTRHigh stroma fibroblasts control the invasion pattern of oral squamous cell carcinoma via ERK5 signaling

Ding

Zhu

et al. 2022

Nat Commun

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The Pattern Of Invasion (POI) of tumor cells into adjacent normal tissues clinically predicts postoperative tumor metastasis/recurrence of early oral squamous cell carcinoma (OSCC), but the mechanisms underlying the development of these subtypes remain unclear. Focusing on the highest score of POIs (Worst POI, WPOI) present within each tumor, we observe a disease progression-driven shift of WPOI towards the high-risk type 4/5, associated with a mesenchymal phenotype in advanced OSCC. WPOI 4-5-derived cancer-associated fibroblasts (CAFsWPOI4-5), characterized by high oxytocin receptor expression (OXTRHigh), contribute to local-regional metastasis. OXTRHigh CAFs induce a desmoplastic stroma and CCL26 is required for the invasive phenotype of CCR3+ tumors. Mechanistically, OXTR activates nuclear ERK5 transcription signaling via Gαq and CDC37 to maintain high levels of OXTR and CCL26. ERK5 ablation reprograms the pro-invasive phenotype of OXTRHigh CAFs. Therefore, targeting ERK5 signaling in OXTRHigh CAFs is a potential therapeutic strategy for OSCC patients with WPOI 4-5.

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Section: Discussionmentioning

confidence: 99%

OXTRHigh stroma fibroblasts control the invasion pattern of oral squamous cell carcinoma via ERK5 signaling

Ding

Zhu

et al. 2022

Nat Commun

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“…In the activated subtype, myCAFs show expression consistent with secreted INHBA which is involved in the SMAD2/SMAD3 pathway in the epithelium. Additionally, the cancer progression and chemoresistance-related OXT/OXTR (oxytocin) genes were highly expressed between CAFs and the neoplastic cells 48 . Myofibroblast CAFs (myCAFs) and endothelial TGFBR1 were identified as a potential targets for TGFB2 from basal-like tumor cells 49 .…”

Section: Resultsmentioning

confidence: 99%

Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype

Oh,

Yoo,

Torre-Healy

et al. 2023

Nat Commun

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Bulk analyses of pancreatic ductal adenocarcinoma (PDAC) samples are complicated by the tumor microenvironment (TME), i.e. signals from fibroblasts, endocrine, exocrine, and immune cells. Despite this, we and others have established tumor and stroma subtypes with prognostic significance. However, understanding of underlying signals driving distinct immune and stromal landscapes is still incomplete. Here we integrate 92 single cell RNA-seq samples from seven independent studies to build a reproducible PDAC atlas with a focus on tumor-TME interdependence. Patients with activated stroma are synonymous with higher myofibroblastic and immunogenic fibroblasts, and furthermore show increased M2-like macrophages and regulatory T-cells. Contrastingly, patients with ‘normal’ stroma show M1-like recruitment, elevated effector and exhausted T-cells. To aid interoperability of future studies, we provide a pretrained cell type classifier and an atlas of subtype-based signaling factors that we also validate in mouse data. Ultimately, this work leverages the heterogeneity among single-cell studies to create a comprehensive view of the orchestra of signaling interactions governing PDAC.

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“…Increased levels of OXTR mRNA were correlated with the occurrence of other cancers. Namely, the expression of this gene was up to 10-fold up-regulated in pancreatic cancer cells [ 137 ], and increased levels of the corresponding mRNA were noted in colorectal cancer [ 138 ]. Moreover, OXTR has been proposed to play a role in breast cancer development and progression, though mechanism(s) of this connection remain(s) to be elucidated [ 139 ].…”

Section: Oxtr In Cancermentioning

confidence: 99%

Roles of the Oxytocin Receptor (OXTR) in Human Diseases

Pierzynowska

Gaffke

Żabińska

et al. 2023

IJMS

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The oxytocin receptor (OXTR), encoded by the OXTR gene, is responsible for the signal transduction after binding its ligand, oxytocin. Although this signaling is primarily involved in controlling maternal behavior, it was demonstrated that OXTR also plays a role in the development of the nervous system. Therefore, it is not a surprise that both the ligand and the receptor are involved in the modulation of behaviors, especially those related to sexual, social, and stress-induced activities. As in the case of every regulatory system, any disturbances in the structures or functions of oxytocin and OXTR may lead to the development or modulation of various diseases related to the regulated functions, which in this case include either mental problems (autism, depression, schizophrenia, obsessive-compulsive disorders) or those related to the functioning of reproductive organs (endometriosis, uterine adenomyosis, premature birth). Nevertheless, OXTR abnormalities are also connected to other diseases, including cancer, cardiac disorders, osteoporosis, and obesity. Recent reports indicated that the changes in the levels of OXTR and the formation of its aggregates may influence the course of some inherited metabolic diseases, such as mucopolysaccharidoses. In this review, the involvement of OXTR dysfunctions and OXTR polymorphisms in the development of different diseases is summarized and discussed. The analysis of published results led us to suggest that changes in OXTR expression and OXTR abundance and activity are not specific to individual diseases, but rather they influence processes (mostly related to behavioral changes) that might modulate the course of various disorders. Moreover, a possible explanation of the discrepancies in the published results of effects of the OXTR gene polymorphisms and methylation on different diseases is proposed.

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Oxytocin and oxytocin receptor alterations, decreased survival, and increased chemoresistance in patients with pancreatic cancer

Cited by 5 publications

References 45 publications

OXTRHigh stroma fibroblasts control the invasion pattern of oral squamous cell carcinoma via ERK5 signaling

OXTRHigh stroma fibroblasts control the invasion pattern of oral squamous cell carcinoma via ERK5 signaling

Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype

Roles of the Oxytocin Receptor (OXTR) in Human Diseases

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