A nuclear cAMP microdomain suppresses tumor growth by Hippo pathway inactivation

Dróżdż, M.; Doane, Ashley S.; Alkallas, Rached; Desman, Garrett; Bareja, Rohan; Reilly, Michael; Bang, Jakyung; Yusupova, Maftuna; You, Jaewon; Eraslan, Zuhal; Wang, Jenny Z.; Verma, Akanksha; Aguirre, Kelsey; Kane, Elsbeth; Watson, Ian R.; Elemento, Olivier; Piskounova, Elena; Merghoub, Taha; Zippin, Jonathan H.

doi:10.1016/j.celrep.2022.111412

Cited by 7 publications

(3 citation statements)

References 97 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In healthy cells, the acidic microenvironment promotes the degradation of the extracellular matrix, while in neoplastic cells low pH facilitates invasive growth and metastasis [ 116 ]. It has been suggested that sAC, as an intracellular pH and metabolic sensor, may play role in a tumorigenesis, since cellular pH and metabolism strongly correlate to tumor proliferation and metastatic spread [ 117 ] Studies have shown that sAC expression is diminished in many solid and hematologic human cancers, including embryonic carcinoma, teratoma, seminoma, yolk sac tumor, some types of leukemia, and others [ 118 ]. Preliminary data on animal and cell line models demonstrated that loss of sAC activity enhances cellular transformation in vitro, activates the MAP kinase signaling pathway, and induces tumorigenesis [ 118 , 119 ].…”

Section: Signal Transduction Pathways As Potential Therapeutic Targetsmentioning

confidence: 99%

cAMP-Dependent Signaling and Ovarian Cancer

Kilanowska

Ziółkowska

Stasiak

et al. 2022

Cells

View full text Add to dashboard Cite

cAMP-dependent pathway is one of the most significant signaling cascades in healthy and neoplastic ovarian cells. Working through its major effector proteins—PKA and EPAC—it regulates gene expression and many cellular functions. PKA promotes the phosphorylation of cAMP response element-binding protein (CREB) which mediates gene transcription, cell migration, mitochondrial homeostasis, cell proliferation, and death. EPAC, on the other hand, is involved in cell adhesion, binding, differentiation, and interaction between cell junctions. Ovarian cancer growth and metabolism largely depend on changes in the signal processing of the cAMP-PKA-CREB axis, often associated with neoplastic transformation, metastasis, proliferation, and inhibition of apoptosis. In addition, the intracellular level of cAMP also determines the course of other pathways including AKT, ERK, MAPK, and mTOR, that are hypo- or hyperactivated among patients with ovarian neoplasm. With this review, we summarize the current findings on cAMP signaling in the ovary and its association with carcinogenesis, multiplication, metastasis, and survival of cancer cells. Additionally, we indicate that targeting particular stages of cAMP-dependent processes might provide promising therapeutic opportunities for the effective management of patients with ovarian cancer.

show abstract

Section: Signal Transduction Pathways As Potential Therapeutic Targetsmentioning

confidence: 99%

cAMP-Dependent Signaling and Ovarian Cancer

Kilanowska

Ziółkowska

Stasiak

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…However, it is noteworthy that cytoplasmic ATP induces structural alterations in GLUT, inhibiting glucose uptake [ 54 ], which can potentially impede cell proliferation in cancer. Additionally, cyclic AMP (cAMP), a product of adenylyl cyclase, suppresses tumor growth in various human cancers [ 55 ]. The decrease in cAMP production may be associated with inhibiting tumor suppressor functions.…”

Section: Discussionmentioning

confidence: 99%

Differentially expressed genes associated with high metabolic tumor volume served as diagnostic markers and potential therapeutic targets for pancreatic cancer

Kim,

Lee,

Jang

et al. 2024

J Transl Med

View full text Add to dashboard Cite

Background The lack of distinct biomarkers for pancreatic cancer is a major cause of early-stage detection difficulty. The pancreatic cancer patient group with high metabolic tumor volume (MTV), one of the values measured from positron emission tomography—a confirmatory method and standard care for pancreatic cancer, showed a poorer prognosis than those with low MTV. Therefore, MTV-associated differentially expressed genes (DEGs) may be candidates for distinctive markers for pancreatic cancer. This study aimed to evaluate the possibility of MTV-related DEGs as markers or therapeutic targets for pancreatic cancer. Methods Tumor tissues and their normal counterparts were obtained from patients undergoing preoperative 18F-FDG PET/CT. The tissues were classified into MTV-low and MTV-high groups (7 for each) based on the MTV2.5 value of 4.5 (MTV-low: MTV2.5 < 4.5, MTV-high: MTV2.5 ≥ 4.5). Gene expression fold change was first calculated in cancer tissue compared to its normal counter and then compared between low and high MTV groups to obtain significant DEGs. To assess the suitability of the DEGs for clinical application, the correlation of the DEGs with tumor grades and clinical outcomes was analyzed in TCGA-PAAD, a large dataset without MTV information. Results Total RNA-sequencing (MTV RNA-Seq) revealed that 44 genes were upregulated and 56 were downregulated in the high MTV group. We selected the 29 genes matching MTV RNA-seq patterns in the TCGA-PAAD dataset, a large clinical dataset without MTV information, as MTV-associated genes (MAGs). In the analysis with the TCGA dataset, MAGs were significantly associated with patient survival, treatment outcomes, TCGA-PAAD-suggested markers, and CEACAM family proteins. Some MAGs showed an inverse correlation with miRNAs and were confirmed to be differentially expressed between normal and cancerous pancreatic tissues. Overexpression of KIF11 and RCC1 and underexpression of ADCY1 and SDK1 were detected in ~ 60% of grade 2 pancreatic cancer patients and associated with ~ 60% mortality in stages I and II. Conclusions MAGs may serve as diagnostic markers and miRNA therapeutic targets for pancreatic cancer. Among the MAGs, KIF11, RCC1, ADCY, and SDK1 may be early diagnostic markers.

show abstract

“…Alternatively, cAMP activates Lats first, then Lats phosphorylates YAP on Ser381 during neurological development 49 . Moreover, nuclear cAMP phosphorylates nuclear YAP at serine 397, resulting in the nuclear exclusion of YAP during tumorigenesis 50 . However, some studies have different conclusions.…”

Section: Discussionmentioning

confidence: 99%

GRK2 mediated degradation of SAV1 initiates hyperplasia of fibroblast-like synoviocytes in rheumatoid arthritis

Guo,

Jiang,

Chu

et al. 2024

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

A nuclear cAMP microdomain suppresses tumor growth by Hippo pathway inactivation

Cited by 7 publications

References 97 publications

cAMP-Dependent Signaling and Ovarian Cancer

cAMP-Dependent Signaling and Ovarian Cancer

Differentially expressed genes associated with high metabolic tumor volume served as diagnostic markers and potential therapeutic targets for pancreatic cancer

GRK2 mediated degradation of SAV1 initiates hyperplasia of fibroblast-like synoviocytes in rheumatoid arthritis

Contact Info

Product

Resources

About