Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ERBB receptor transmodulation by heterologous G-protein-coupled receptors (GPCR) generates functional diversity in signal transduction. Tachykinins are neuropeptides and proinflammatory cytokines that promote cell survival and cancer progression by activating several GPCRs. In this work, we found that the pain-associated tachykinin Substance P (SP) contributes to persistent transmodulation of the ERBB receptors, EGFR and HER2, in breast cancer, acting to enhance malignancy and therapeutic resistance. SP and its high-affinity receptor NK-1R were highly expressed in HER2(+) primary breast tumors (relative to the luminal and triple-negative subtypes) and were overall correlated with poor prognosis factors. In breast cancer cell lines and primary cultures derived from breast cancer samples, we found that SP could activate HER2. Conversely, RNA interference-mediated attenuation of NK-1R, or its chemical inhibition, or suppression of overall GPCR-mediated signaling, all strongly decreased steady-state expression of EGFR and HER2, establishing that their basal activity relied upon transdirectional activation by GPCR. Thus, SP exposure affected cellular responses to anti-ERBB therapies. Our work reveals an important oncogenic cooperation between NK-1R and HER2, thereby adding a novel link between inflammation and cancer progression that may be targetable by SP antagonists that have been clinically explored.
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PMID:Substance P autocrine signaling contributes to persistent HER2 activation that drives malignant progression and drug resistance in breast cancer. 2403 Sep 79

Breast cancer is the second leading cause of cancer death in women with increasing incidence. Hence, finding a diagnostic factor and/or potential drug target could lead to an earlier diagnosis or a more effective therapeutic protocol. It is shown that substance P (SP) through its receptor neurokinin-1 (NK1R) could initiate tumor cell proliferation, angiogenesis, and migration. This was a case-control study on 41 women with breast cancer and 34 healthy controls. Serum level of SP was measured using an ELISA method, and immunohistochemistry staining was performed to study NK1R expression in different cell compartments. Assessing serum SP values of patients showed significantly higher levels than those of healthy individuals. However, no significant correlation was found between SP levels and tumor criteria, but between SP and HER-2. Moreover, the percentage, intensity of staining as well as tissue distribution of NK1R were significantly higher in tumor tissues as compared with controls. Increased serum SP levels and NK1R tissue distribution were observed in patients with breast cancer as compared with their controls, highlighting the involvement of SP/NK1R complex in breast cancer incidence. NK1R profound expression in tumor cell cytoplasm and its significant correlation with the majority of cancer features can be of importance to be taken into consideration as a possible potential therapeutic target in future targeted therapeutic strategies. Furthermore, cytoplasmic expression of NK1R can be suggested as a potent prognostic factor as it has shown significant correlation with TNM and tumor grade.
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PMID:Evaluation of serum level of substance P and tissue distribution of NK-1 receptor in breast cancer. 3068 88

Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer death among females. BC cells not showing HER-2/Neu amplification and not expressing estrogen/ progesterone receptors are named triple-negative BC (TNBC) cells. TNBC represents 10-15% of all BC and is associated with an aggressive clinical course. TNBC patient prognosis, survival and response to current therapies are poor and for this reason, it is crucial to search for new therapeutic targets in TNBC to develop new therapeutic strategies. One of these targets is the neurokinin-1 receptor (NK-1R). It is well known that the substance P (SP)/NK-1R system is involved in cancer progression. TNBC cells overexpress the NK-1R and, after binding to this receptor, SP promotes the proliferation/ migration of TNBC cells. Non-peptide NK-1R antagonists (e.g., aprepitant) are known to exert, via the NK-1R, an antitumor action; TNBC cells die by apoptosis. In this review, we update the data on a promising therapeutic innovation: the use of NK-1R antagonists for the treatment of TNBC patients.
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PMID:Triple Negative Breast Cancer: How Neurokinin-1 Receptor Antagonists Could Be Used as a New Therapeutic Approach. 3172 1