Oxidative stress‐induced <scp>FAK</scp> activation contributes to uterine serous carcinoma aggressiveness

López-Mejía, Isabel C.; Pijuan, Jordi; Navaridas, Raúl; Santacana, Marı́a; Gatius, Sònia; Velasco, Ana; Castellà, Gerard; Panosa, Anaïs; Cabiscol, Elisa; Pinyol, Miquel; Coll, Laura; Bonifaci, Núria; Peña, Laura Plata; Vidal, August; Villanueva, Alberto; Garí, Eloi; Llobet‐Navas, David; Fajas, Lluís; Matías‐Guiu, Xavier; Yeramian, Andrée

doi:10.1002/1878-0261.13346

Cited by 10 publications

(2 citation statements)

References 68 publications

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“…This heightened oxidative stress leads to the phosphorylation of FAK, facilitating tumor invasion and metastasis through the ROS-FAK-PAX signaling pathway. Defactinib significantly inhibited the growth of the tumors of patient-derived orthotopic xenograft models in this context, emphasizing the potential of FAK inhibition in the treatment of USC ( Lopez-Mejia et al, 2023 ).…”

Section: Development and Clinical Research Progress Of Fak Inhibitorsmentioning

confidence: 86%

Roles and inhibitors of FAK in cancer: current advances and future directions

Hu,

Wang,

Shang

et al. 2024

Front. Pharmacol.

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Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that exhibits high expression in various tumors and is associated with a poor prognosis. FAK activation promotes tumor growth, invasion, metastasis, and angiogenesis via both kinase-dependent and kinase-independent pathways. Moreover, FAK is crucial for sustaining the tumor microenvironment. The inhibition of FAK impedes tumorigenesis, metastasis, and drug resistance in cancer. Therefore, developing targeted inhibitors against FAK presents a promising therapeutic strategy. To date, numerous FAK inhibitors, including IN10018, defactinib, GSK2256098, conteltinib, and APG-2449, have been developed, which have demonstrated positive anti-tumor effects in preclinical studies and are undergoing clinical trials for several types of tumors. Moreover, many novel FAK inhibitors are currently in preclinical studies to advance targeted therapy for tumors with aberrantly activated FAK. The benefits of FAK degraders, especially in terms of their scaffold function, are increasingly evident, holding promising potential for future clinical exploration and breakthroughs. This review aims to clarify FAK’s role in cancer, offering a comprehensive overview of the current status and future prospects of FAK-targeted therapy and combination approaches. The goal is to provide valuable insights for advancing anti-cancer treatment strategies.

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Section: Development and Clinical Research Progress Of Fak Inhibitorsmentioning

confidence: 86%

Roles and inhibitors of FAK in cancer: current advances and future directions

Hu,

Wang,

Shang

et al. 2024

Front. Pharmacol.

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“…PKN1 activation levels were assessed via Western blot technique using an anti-Phospho-PRK1 (Thr774)/PRK2 (Thr816) antibody. Cells were washed with cold PBS and either lysed with NP-40 buffer supplemented with Proteases and Phosphatases inhibitors or with SDS lysis buffer (2% SDS, 125 mM Tris–HCL pH6.8), and lysates were subjected to Western blotting, as described in a previous work [ 17 ]. Equal amounts of proteins were resolved in 10–15% SDS-PAGE gels and transferred to PVDF membranes (Millipore, Bedford, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

PKN1 Kinase: A Key Player in Adipocyte Differentiation and Glucose Metabolism

et al. 2023

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Adipocyte dysfunction is the driver of obesity and correlates with insulin resistance and the onset of type 2 diabetes. Protein kinase N1 (PKN1) is a serine/threonine kinase that has been shown to contribute to Glut4 translocation to the membrane and glucose transport. Here, we evaluated the role of PKN1 in glucose metabolism under insulin-resistant conditions in primary visceral adipose tissue (VAT) from 31 patients with obesity and in murine 3T3-L1 adipocytes. In addition, in vitro studies in human VAT samples and mouse adipocytes were conducted to investigate the role of PKN1 in the adipogenic maturation process and glucose homeostasis control. We show that insulin-resistant adipocytes present a decrease in PKN1 activation levels compared to nondiabetic control counterparts. We further show that PKN1 controls the adipogenesis process and glucose metabolism. PKN1-silenced adipocytes present a decrease in both differentiation process and glucose uptake, with a concomitant decrease in the expression levels of adipogenic markers, such as PPARγ, FABP4, adiponectin and CEBPα. Altogether, these results point to PKN1 as a regulator of key signaling pathways involved in adipocyte differentiation and as an emerging player of adipocyte insulin responsiveness. These findings may provide new therapeutic approaches for the management of insulin resistance in type 2 diabetes.

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