STAT3 signaling in ovarian cancer: a potential therapeutic target

Liang, Renba; Chen, Xishan; Chen, Li; Wan, Fangzhu; Chen, Kaihua; Sun, Yongchu; Zhu, Xiaodong

doi:10.7150/jca.35011

Cited by 76 publications

(63 citation statements)

References 180 publications

(192 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of such STAT3 interacting molecules is CD44. As with CD44, STAT3 signaling has been frequently implicated in ovarian cancer metastasis, therapy resistance, and CSC maintenance ( 64 , 65 ). STAT3 transcriptional activity has been demonstrated to drive the migration and invasiveness of ovarian cancer ( 66 – 68 ).…”

Section: Cd44 and Stat3 Crosstalk In Cancermentioning

confidence: 99%

CD44 in Ovarian Cancer Progression and Therapy Resistance—A Critical Role for STAT3

Martincuks

Zhao

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Despite significant progress in cancer therapy over the last decades, ovarian cancer remains the most lethal gynecologic malignancy worldwide with the five-year overall survival rate less than 30% due to frequent disease recurrence and chemoresistance. CD44 is a non-kinase transmembrane receptor that has been linked to cancer metastatic progression, cancer stem cell maintenance, and chemoresistance development via multiple mechanisms across many cancers, including ovarian, and represents a promising therapeutic target for ovarian cancer treatment. Moreover, CD44-mediated signaling interacts with other well-known pro-tumorigenic pathways and oncogenes during cancer development, such as signal transducer and activator of transcription 3 (STAT3). Given that both CD44 and STAT3 are strongly implicated in the metastatic progression and chemoresistance of ovarian tumors, this review summarizes currently available evidence about functional crosstalk between CD44 and STAT3 in human malignancies with an emphasis on ovarian cancer. In addition to the role of tumor cell-intrinsic CD44 and STAT3 interaction in driving cancer progression and metastasis, we discuss how CD44 and STAT3 support the pro-tumorigenic tumor microenvironment and promote tumor angiogenesis, immunosuppression, and cancer metabolic reprogramming in favor of cancer progression. Finally, we review the current state of therapeutic CD44 targeting and propose superior treatment possibilities for ovarian cancer.

show abstract

Section: Cd44 and Stat3 Crosstalk In Cancermentioning

confidence: 99%

CD44 in Ovarian Cancer Progression and Therapy Resistance—A Critical Role for STAT3

Martincuks

Zhao

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Taken together, our data confirm previous reports, which showed that FASN inhibition interferes with protein synthesis and promotes protein degradation, resulting in lower protein steady state levels 4,9,13 . Moreover, insulin-, epidermal-and hepatocyte-growth factor receptors and their downstream effectors (CBL, CRK, EGFR, ERBB2, GRB2, MAPKs, RAS family members), as well as STAT3, which regulate carbohydrate utilization, growth, migration and invasion 19,20 , were downregulated by G28UCM in SKOV3 and/or OVCAR3 (Table 2 and Supplemental Table S3).…”

Section: G28ucm Affects Protein Synthesis and Cell Growth Signalling mentioning

confidence: 99%

Membrane disruption, but not metabolic rewiring, is the key mechanism of anticancer-action of FASN-inhibitors: a multi-omics analysis in ovarian cancer

Grunt

Slany

Semkova

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Fatty-acid(FA)-synthase(FASN) is a druggable lipogenic oncoprotein whose blockade causes metabolic disruption. Whether drug-induced metabolic perturbation is essential for anticancer drug-action, or is just a secondary—maybe even a defence response—is still unclear. To address this, SKOV3 and OVCAR3 ovarian cancer(OC) cell lines with clear cell and serous histology, two main OC subtypes, were exposed to FASN-inhibitor G28UCM. Growth-inhibition was compared with treatment-induced cell-metabolomes, lipidomes, proteomes and kinomes. SKOV3 and OVCAR3 were equally sensitive to low-dose G28UCM, but SKOV3 was more resistant than OVCAR3 to higher concentrations. Metabolite levels generally decreased upon treatment, but individual acylcarnitines, glycerophospholipids, sphingolipids, amino-acids, biogenic amines, and monosaccharides reacted differently. Drug-induced effects on central-carbon-metabolism and oxidative-phosphorylation (OXPHOS) were essentially different in the two cell lines, since drug-naïve SKOV3 are known to prefer glycolysis, while OVCAR3 favour OXPHOS. Moreover, drug-dependent increase of desaturases and polyunsaturated-fatty-acids (PUFAs) were more pronounced in SKOV3 and appear to correlate with G28UCM-tolerance. In contrast, expression and phosphorylation of proteins that control apoptosis, FA synthesis and membrane-related processes (beta-oxidation, membrane-maintenance, transport, translation, signalling and stress-response) were concordantly affected. Overall, membrane-disruption and second-messenger-silencing were crucial for anticancer drug-action, while metabolic-rewiring was only secondary and may support high-dose-FASN-inhibitor-tolerance. These findings may guide future anti-metabolic cancer intervention.

show abstract

“…The oncogene, signal transducer and activator of transcription 3 (STAT3), is found constitutively activated in many human malignancies (Levy and Inghirami, 2006;Zhang and Lai, 2014;Guanizo et al, 2018). Activated STAT3 regulates a variety of tumor cell processes, such as tumor cell growth, survival, invasion, cancer stemness, and chemoresistance, and has been shown to contribute to disease aggressiveness in ovarian cancer (Saini et al, 2017;Liang et al, 2020;Wu et al, 2020). Constitutively active STAT3 up-regulates the survival factors, Bcl-2 and Bcl-xL, whilst inhibiting apoptosis via induction of AKT (Siddiquee and Turkson, 2008).…”

Section: Introductionmentioning

confidence: 99%

Krupple-Like Factor 5 is a Potential Therapeutic Target and Prognostic Marker in Epithelial Ovarian Cancer

et al. 2020

View full text Add to dashboard Cite

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. Despite current therapeutic and surgical options, advanced EOC shows poor prognosis. Identifying novel molecular therapeutic targets is highly needed in the management of EOC. Krupple-like factor 5 (KLF5), a zinc-finger transcriptional factor, is highly expressed in a variety of cancer types. However, its role and expression in EOC is not fully illustrated. Immunohistochemical analysis was performed to assess KLF5 protein expression in 425 primary EOC samples using tissue microarray. We also addressed the function of KLF5 in EOC and its interaction with signal transducer and activator of transcription 3 (STAT3) signaling pathway. We found that KLF5 overexpressed in 53% (229/425) of EOC samples, and is associated with aggressive markers. Forced expression of KLF5 enhanced cell growth in low expressing EOC cell line, MDAH2774. Conversely, knockdown of KLF5 reduced cell growth, migration, invasion and progression of epithelial to mesenchymal transition in KLF5 expressing cell lines, OVISE and OVSAHO. Importantly, silencing of KLF5 decreased the self-renewal ability of spheroids generated from OVISE and OVSAHO cell lines. In addition, downregulation of KLF5 potentiated the effect of cisplatin to induce apoptosis in these cell lines. These data reveals the pro-tumorigenic role of KLF5 in EOC and uncover its role in activation of STAT3 signaling pathway, suggesting the importance of KLF5 as a potential therapeutic target for EOC therapy.

show abstract

STAT3 signaling in ovarian cancer: a potential therapeutic target

Cited by 76 publications

References 180 publications

CD44 in Ovarian Cancer Progression and Therapy Resistance—A Critical Role for STAT3

CD44 in Ovarian Cancer Progression and Therapy Resistance—A Critical Role for STAT3

Membrane disruption, but not metabolic rewiring, is the key mechanism of anticancer-action of FASN-inhibitors: a multi-omics analysis in ovarian cancer

Krupple-Like Factor 5 is a Potential Therapeutic Target and Prognostic Marker in Epithelial Ovarian Cancer

Contact Info

Product

Resources

About