KISS1/KISS1R and Breast Cancer: Metastasis Promoter

Guzman, Stephania; Brackstone, Muriel; Wondisford, Frederic E.; Babwah, Andy V.; Bhattacharya, Moshmi

doi:10.1055/s-0039-3400968

Cited by 12 publications

(13 citation statements)

References 101 publications

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“…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

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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.

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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

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“…Our earlier work has shown that, in triple-negative breast cancer (TNBC), KISS1R signaling promotes tumor growth and metastasis ( 70 ). When ERα is reexpressed in TNBC cells, KISS1R is downregulated, demonstrating that ERα negatively regulates KISS1R expression in TNBC ( 85 ). In native TNBC cells lacking ERα, KISS1R signaling promotes epithelial-mesenchymal transition, MAPK activation, and cancer growth and invasion ( 70 , 86 – 88 ).…”

Section: Discussionmentioning

confidence: 99%

Targeting hepatic kisspeptin receptor ameliorates nonalcoholic fatty liver disease in a mouse model

Guzman¹,

Dragan²,

Kwon³

et al. 2022

Journal of Clinical Investigation

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Nonalcoholic fatty liver disease (NAFLD), the most common liver disease, has become a silent worldwide pandemic. The incidence of NAFLD correlates with the rise in obesity, type 2 diabetes, and metabolic syndrome. A hallmark featureof NAFLD is excessive hepatic fat accumulation or steatosis, due to dysregulated hepatic fat metabolism, which can progress to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Currently, there are no approved pharmacotherapies to treat this disease. Here, we have found that activation of the kisspeptin 1 receptor (KISS1R) signaling pathway has therapeutic effects in NAFLD. Using high-fat diet–fed mice, we demonstrated that a deletion of hepatic Kiss1r exacerbated hepatic steatosis. In contrast, enhanced stimulation of KISS1R protected against steatosis in wild-type C57BL/6J mice and decreased fibrosis using a diet-induced mouse model of NASH. Mechanistically, we found that hepatic KISS1R signaling activates the master energy regulator, AMPK, to thereby decrease lipogenesis and progression to NASH. In patients with NAFLD and in high-fat diet–fed mice, hepatic KISS1/KISS1R expression and plasma kisspeptin levels were elevated, suggesting a compensatory mechanism to reduce triglyceride synthesis. These findings establish KISS1R as a therapeutic target to treat NASH.

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“…High expression levels of DNMT1 have been associated with silencing of NIS (51). The role of KISS1/KISS1R signaling is controversial in various types of cancers, as it has been associated with both roles in metastatic promotion and suppression (52)(53)(54). Savvidis et al found increased levels of KISS1 in extrathyroidal tissues of advanced differentiated TCs while an inverse correlation between KISS1R and tumor size (55).…”

Section: Dna Methylation In Thyroid Tumorsmentioning

confidence: 99%

Cancer Stem Cells in Thyroid Tumors: From the Origin to Metastasis

et al. 2020

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Thyroid tumors are extremely heterogeneous varying from almost benign tumors with good prognosis as papillary or follicular tumors, to the undifferentiated ones with severe prognosis. Recently, several models of thyroid carcinogenesis have been described, mostly hypothesizing a major role of the thyroid cancer stem cell (TCSC) population in both cancer initiation and metastasis formation. However, the cellular origin of TCSC is still incompletely understood. Here, we review the principal epigenetic mechanisms relevant to TCSC origin and maintenance in both well-differentiated and anaplastic thyroid tumors. Specifically, we describe the alterations in DNA methylation, histone modifiers, and microRNAs (miRNAs) involved in TCSC survival, focusing on the potential of targeting aberrant epigenetic modifications for developing novel therapeutic approaches. Moreover, we discuss the bidirectional relationship between TCSCs and immune cells. The cells of innate and adaptive response can promote the TCSC-driven tumorigenesis, and conversely, TCSCs may favor the expansion of immune cells with protumorigenic functions. Finally, we evaluate the role of the tumor microenvironment and the complex cross-talk of chemokines, hormones, and cytokines in regulating thyroid tumor initiation, progression, and therapy refractoriness. The re-education of the stromal cells can be an effective strategy to fight thyroid cancer. Dissecting the genetic and epigenetic landscape of TCSCs and their interactions with tumor microenvironment cells is urgently needed to select more appropriate treatment and improve the outcome of patients affected by advanced differentiated and undifferentiated thyroid cancers.

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KISS1/KISS1R and Breast Cancer: Metastasis Promoter

Cited by 12 publications

References 101 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

Targeting hepatic kisspeptin receptor ameliorates nonalcoholic fatty liver disease in a mouse model

Cancer Stem Cells in Thyroid Tumors: From the Origin to Metastasis

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