Role of the tumor microenvironment in regulating the anti-metastatic effect of KISS1

Harihar, Sitaram; Ray, Srijit; Narayanan, Samyukta; Santhoshkumar, A; Ly, Thuc; Welch, Danny R.

doi:10.1007/s10585-020-10030-6

Cited by 13 publications

(14 citation statements)

References 135 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Kp regulate gonadotropin secretion in several mammalian species, acting via KISS1R. Numerous studies have delineated the antimetastatic and tumor-suppressant role of Kp/KISS1R signaling, which are found to inhibit nuclear factor kappa B (NF-kB) and mitogen-activated protein kinase (MAPK) signaling pathways [43][44][45][46][47][48]. We demonstrated the in vitro role of Kp via activation of its receptor, KISS1R, in regulating ASM proliferation and observed that cleaved forms of Kp, mainly Kp-10, alleviated PDGF-induced ASM proliferation by regulating the p38/MAPK signaling pathways [24].…”

Section: Discussionmentioning

confidence: 99%

Kisspeptin regulates airway hyperresponsiveness and remodeling in a mouse model of asthma

Borkar

Ambhore

Balraj

et al. 2023

The Journal of Pathology

View full text Add to dashboard Cite

Asthma is a multifactorial disease of origin characterized by airway hyperresponsiveness (AHR) and airway remodeling. Several pieces of evidence from other pathologies suggest that Kisspeptins (Kp) regulate cell proliferation, migration, and invasion, mechanisms that are highly relevant to asthma. Our recent in vitro studies show Kp‐10 (active peptide of Kp), via its receptor, KISS1R, inhibits human airway smooth muscle cell proliferation. Here, we hypothesize a crucial role for Kp‐10 in regulating AHR and airway remodeling in vivo. Utilizing C57BL/6J mice, we assessed the effect of chronic intranasal Kp‐10 exposure on mixed allergen (MA)‐induced mouse model of asthma. MA‐challenged mice showed significant deterioration of lung function compared to those exposed to vehicle (DPBS); Kp‐10 treatment significantly improved the MA‐altered lung functions. Mice treated with Kp‐10 alone did not show any notable changes in lung functions. MA‐exposed mice showed a significant reduction in KISS1R expression as compared to vehicle alone. MA‐challenged mice showed significant alterations in immune cell infiltration in the airways and remodeling changes. Proinflammatory cytokines were significantly increased upon MA exposure, an effect abrogated by Kp‐10 treatment. Furthermore, biochemical and histological studies showed Kp‐10 exposure significantly reduced MA‐induced smooth muscle mass and soluble collagen in the lung. Overall, our findings highlight the effect of chronic Kp‐10 exposure in regulating MA‐induced AHR and remodeling. © 2023 The Pathological Society of Great Britain and Ireland.

show abstract

Section: Discussionmentioning

confidence: 99%

Kisspeptin regulates airway hyperresponsiveness and remodeling in a mouse model of asthma

Borkar

Ambhore

Balraj

et al. 2023

The Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…9g). In xenograft thyroid tumors derived from the subcutaneous injection of mutated D22 TPCs, the intra-tumoral administration of TIMP1 and KISS1R inhibitors [44][45][46] lead to a significant delay in tumor growth, characterized by a marked expression of NIS, and a prolonged percentage of mice survival (Fig. 6H, I).…”

Section: Kiss1r Is a Prognostic Factor And A Potential Therapeutic Ta...mentioning

confidence: 99%

Recapitulating thyroid cancer histotypes through engineering embryonic stem cells

et al. 2023

View full text Add to dashboard Cite

Thyroid carcinoma (TC) is the most common malignancy of endocrine organs. The cell subpopulation in the lineage hierarchy that serves as cell of origin for the different TC histotypes is unknown. Human embryonic stem cells (hESCs) with appropriate in vitro stimulation undergo sequential differentiation into thyroid progenitor cells (TPCs-day 22), which maturate into thyrocytes (day 30). Here, we create follicular cell-derived TCs of all the different histotypes based on specific genomic alterations delivered by CRISPR-Cas9 in hESC-derived TPCs. Specifically, TPCs harboring BRAFV600E or NRASQ61R mutations generate papillary or follicular TC, respectively, whereas addition of TP53R248Q generate undifferentiated TCs. Of note, TCs arise by engineering TPCs, whereas mature thyrocytes have a very limited tumorigenic capacity. The same mutations result in teratocarcinomas when delivered in early differentiating hESCs. Tissue Inhibitor of Metalloproteinase 1 (TIMP1)/Matrix metallopeptidase 9 (MMP9)/Cluster of differentiation 44 (CD44) ternary complex, in cooperation with Kisspeptin receptor (KISS1R), is involved in TC initiation and progression. Increasing radioiodine uptake, KISS1R and TIMP1 targeting may represent a therapeutic adjuvant option for undifferentiated TCs.

show abstract

“…It is known that kisspeptin is expressed in the hypothalamus where affects the hypothalamic-pituitary-gonadal axis and reproductive function by regulating gonadotropin-releasing hormone (GnRH) secretion [ 27 ]. In addition, kisspeptin plays important role in the pathogenesis of various human cancers [ 28 , 29 ]. To date, most of the mechanisms that mediate the regulation of KISS1 gene expression are identified in the hypothalamic context of animal models and cancers.…”

Section: Discussionmentioning

confidence: 99%

TGF-β1 inhibits human trophoblast cell invasion by upregulating kisspeptin expression through ERK1/2 but not SMAD signaling pathway

Fang

Yang

Gao

et al. 2022

Reprod Biol Endocrinol

View full text Add to dashboard Cite

Background Tightly regulation of extravillous cytotrophoblast (EVT) cell invasion is critical for the placentation and establishment of a successful pregnancy. Insufficient EVT cell invasion leads to the development of preeclampsia (PE) which is a leading cause of maternal and perinatal mortality and morbidity. Transforming growth factor-beta1 (TGF-β1) and kisspeptin are expressed in the human placenta and have been shown to inhibit EVT cell invasion. Kisspeptin is a downstream target of TGF-β1 in human breast cancer cells. However, whether kisspeptin is regulated by TGF-β1 and mediates TGF-β1-suppressed human EVT cell invasion remains unclear. Methods The effect of TGF-β1 on kisspeptin expression and the underlying mechanisms were explored by a series of in vitro experiments in a human EVT cell line, HTR-8/SVneo, and primary cultures of human EVT cells. Serum levels of TGF-β1 and kisspeptin in patients with or without PE were measured by ELISA. Results TGF-β1 upregulates kisspeptin expression in HTR-8/SVneo cells and primary cultures of human EVT cells. Using pharmacological inhibitor and siRNA, we demonstrate that the stimulatory effect of TGF-β1 on kisspeptin expression is mediated via the ALK5 receptor. Treatment with TGF-β1 activates SMAD2/3 canonical pathways as well as ERK1/2 and PI3K/AKT non-canonical pathways. However, only inhibition of ERK1/2 activation attenuates the stimulatory effect of TGF-β1 on kisspeptin expression. In addition, siRNA-mediated knockdown of kisspeptin attenuated TGF-β1-suppressed EVT cell invasion. Moreover, we report that serum levels of TGF-β1 and kisspeptin are significantly upregulated in patients with PE. Conclusions By illustrating the potential physiological role of TGF-β1 in the regulation of kisspeptin expression, our results may serve to improve current strategies used to treat placental diseases.

show abstract

Role of the tumor microenvironment in regulating the anti-metastatic effect of KISS1

Cited by 13 publications

References 135 publications

Kisspeptin regulates airway hyperresponsiveness and remodeling in a mouse model of asthma

Kisspeptin regulates airway hyperresponsiveness and remodeling in a mouse model of asthma

Recapitulating thyroid cancer histotypes through engineering embryonic stem cells

TGF-β1 inhibits human trophoblast cell invasion by upregulating kisspeptin expression through ERK1/2 but not SMAD signaling pathway

Contact Info

Product

Resources

About