The substance P/NK-1 receptor system: NK-1 receptor antagonists as anti-cancer drugs

Muñoz, Miguel; Coveñas, Rafael; Esteban, Francisco; Redondo, Maximino

doi:10.1007/s12038-015-9530-8

Cited by 89 publications

(123 citation statements)

References 130 publications

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“…In this report, our results showed that SP and NK‐1R were expressed at high protein levels in GBC tumor samples. Consistent with previous researches, the activation of NK‐1R dose‐dependently induced the proliferation and invasion of GBC cells, and these effects could be blocked by NK‐1R antagonist. Notably, we also observed that NK‐1R could significantly increase the activity of NF‐κB throuth up‐regulating Akt.…”

Section: Discussionsupporting

confidence: 90%

“…Over the past decades, the function of peptides and their receptors in tumors have attracted growing interest, and research efforts show that these peptides and receptors can influence cancer progress. One such target could be SP/NK‐1R system, since it is known that NK‐1R can act as a mitogen on several human cancers . Currently, it is still unknown whether NK‐1R exists the same effect in GBC.…”

Section: Discussionmentioning

confidence: 99%

“…The transient increasing of these messages will trigger a cascade of protein phosphorylation/dephosphorylation reactions, which are critical for gene expression and cell function . This interaction occurs in various physiologic and pathophysiologic responses which are mediated by NK‐1R, such as sensory perception, emesis, neuronal degeneration, inflammation, wound healing, pain, anxiety, and the regulation of the cardiovascular system . In addition, NK‐1R has also been reported to be over‐expressed in many human cancer cells, as well as in primary tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Most importantly, NK‐1R regulates many biological functions in neurogenic inflammation, immune responses, pain and depression. And it has also been implicated to play a vital role in regulating numerous pathophysiological actions related to cancer . After combining specifically with the SP, one of the tachykinins, NK‐1R controls the tumor cell proliferation, migration, metastasis and angiogenesis .…”

Section: Introductionmentioning

confidence: 99%

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SP/NK‐1R promotes gallbladder cancer cell proliferation and migration

Deng

Tang

et al. 2019

J Cellular Molecular Medi

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Aberrant substance P/neurokinin‐1 receptor (SP/NK‐1R) system activation plays a critical role in various disorders, however, little is known about the expression and the detailed molecular mechanism of the SP and NK‐1R in gallbladder cancer (GBC). In this study, we firstly analyzed the expression and clinical significance of them in patients with GBC. Then, cellular assays were performed to clarify their biological role in GBC cells. Moreover, we investigated the molecular mechanisms regulated by SP/NK‐1R. Meanwhile, mice xenografted with human GBC cells were analyzed regarding the effects of SP/NK1R complex in vivo. Finally, patient samples were utilized to investigate the effect of SP/NK‐1R. The results showed that SP and NK‐1R were highly expressed in GBC. We found that SP strongly induced GBC cell proliferation, clone formation, migration and invasion, whereas antagonizing NK‐1R resulted in the opposite effects. Moreover, SP significantly enhanced the expression of NF‐κB p65 and the tumor‐associated cytokines, while, Akt inhibitor could reverse these effects. Further studies indicated that decreasing activation of NF‐κB or Akt diminished GBC cell proliferation and migration. In consistent with results, immunohistochemical staining showed high levels of Akt, NF‐κB and cytokines in tumor tissues. Most importantly, the similar conclusion was obtained in xenograft mouse model. Our findings demonstrate that NK‐1R, after binding with the endogenous agonist SP, could induce GBC cell migration and spreading via modulation of Akt/NF‐κB pathway.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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SP/NK‐1R promotes gallbladder cancer cell proliferation and migration

Deng

Tang

et al. 2019

J Cellular Molecular Medi

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“…15 Notably, these effects mediated by SP can be suppressed by NK-1R antagonists. 16 It was reported that SP/NK-1R signaling plays an important role in cancer progression and metastasis, and SP could function as a mitogen in NK-1R expressing tumor cells. 14 For example, SP induced the expression of matrix metalloproteinase 2 (MMP-2) in pancreatic cancer cells, and NK-1R antagonists inhibited MMP-2 expression.…”

mentioning

confidence: 99%

Substance P Promotes the Progression of Endometrial Adenocarcinoma

Ma¹,

Yuan²,

Cheng

et al. 2016

Int J Gynecol Cancer

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Neuropeptides in Cancer: Friend and Foe?

Berisha

Borniger

2022

Advanced Biology

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highly dynamic network of various cell types (e.g., cancer cells, endothelial cells, immune cells, fibroblasts) that exert differential effects on neuronal activity within the local environment. Thus, complex signaling between cancer and stromal cells in the TME results in altered firing rates of local nerves. Reciprocally, increased neuronal activity and subsequent release of classical neurotransmitters and/or neuropeptides within the TME results in enhanced cancer progression and subsequent metastasis in various preclinical models and clinical studies. [5][6][7][8][9] Nerves interact with multiple stromal cells in the TME where they indirectly promote tumor growth, progression, and subsequent metastasis. [10] Several studies have demonstrated that sympathetic nerve innervation and subsequent release of the neurotransmitter norepinephrine (NE) is increased in breast tumors. [6,8,9] However, recent work has demonstrated that there is an inverse relationship between tumor weight and norepinephrine content (i.e., larger the size of the tumor, the lower the levels of NE), despite increased innervation of sympathetic nerves within the TME. [11] These findings may be attributed to a relatively unexplored phenomenon: neuropeptide release within the TME. Neuropeptides are molecular messengers that regulate a variety of functions in the central and peripheral nervous systems via binding G-protein-coupled receptors (GPCRs) on target cells. One of the many functions of neuropeptides is serving as growth factors for normal cells via the activation of the heterotrimeric G protein Gq and subsequent synthesis of second messengers and engagement of tyrosine phosphorylation cascades. Neuropeptides act as neuromodulators, in that they can alter the response of neurons to neurotransmitters and other circulating signals, such as leptin, ghrelin, glucose, and insulin-all of which are affected during cancer progression. [12][13][14][15][16][17] For example, both neuropeptide Y (NPY) and hypocretin/orexin neurons appear to mediate some of the orexigenic effects of centrally administered ghrelin as administration of NPY receptor antagonists attenuated ghrelininduced feeding. Similarly, ghrelin-induced feeding was suppressed in orexin knockout mice, indicating that ghrelin may stimulate feeding through both the orexin and NPY systems. [18] However, neuropeptide signaling is exploited within cancer cells and many studies demonstrate the contribution of neuropeptides in tumor cell proliferation and migration, [19] with many major neuropeptides also potentially contributing to cancer processes (see Table 1). Additionally, neuropeptides exert direct Neuropeptides are small regulatory molecules found throughout the body, most notably in the nervous, cardiovascular, and gastrointestinal systems. They serve as neurotransmitters or hormones in the regulation of diverse physiological processes. Cancer cells escape normal growth control mechanisms by altering their expression of growth factors, receptors, or intracellular signals, and neuropeptid...

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The substance P/NK-1 receptor system: NK-1 receptor antagonists as anti-cancer drugs

Cited by 89 publications

References 130 publications

SP/NK‐1R promotes gallbladder cancer cell proliferation and migration

SP/NK‐1R promotes gallbladder cancer cell proliferation and migration

Substance P Promotes the Progression of Endometrial Adenocarcinoma

Neuropeptides in Cancer: Friend and Foe?

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