TY - JOUR
T1 - An update on TWEAK/Fn14 signaling pathway
T2 - A comprehensive review
AU - Sharma, Ujjawal
AU - Mehrotra, Arpit
AU - Sharma, Bunty
AU - Sood, Abhilasha
AU - Sak, Kartin
AU - Haque, Shafiul
AU - Parashar, Nidarshana Chaturvedi
AU - Gupta, Madhu
AU - Tuli, Hardeep Singh
N1 - Publisher Copyright:
© 2025 Elsevier Inc.
PY - 2026/3
Y1 - 2026/3
N2 - Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional protein, present in various cell types and tissues, which, upon binding to the receptor factor-inducible 14 (Fn14), is involved in diverse pathologic processes including cell proliferation and death, angiogenesis, carcinogenesis, and inflammation. Interestingly, any alterations of their intracellular signaling are well correlated with the advancement of several diseases. The expression of TWEAK and Fn14 is augmented in many solid tumors compared with healthy tissues, thus leading to the enhancement of the proliferation, invasion, and subsequent migration of tumor cells. However, few TWEAK/Fn14 targeting pharmacological agents involved in inhibiting the progression of tumors have shown initial success in both clinical and pre-clinical experimental settings. Moreover, such agents improved angiogenesis, pro-inflammatory cytokine expression, and epithelial–mesenchymal transitions, upon TWEAK/Fn14 activation. This review provides an overview of the current understanding of the TWEAK–Fn14 signaling axis, its role in augmenting pathological characteristics of various diseases, and the existence of potential therapeutic targets for the development of novel pharmacological interventions.
AB - Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional protein, present in various cell types and tissues, which, upon binding to the receptor factor-inducible 14 (Fn14), is involved in diverse pathologic processes including cell proliferation and death, angiogenesis, carcinogenesis, and inflammation. Interestingly, any alterations of their intracellular signaling are well correlated with the advancement of several diseases. The expression of TWEAK and Fn14 is augmented in many solid tumors compared with healthy tissues, thus leading to the enhancement of the proliferation, invasion, and subsequent migration of tumor cells. However, few TWEAK/Fn14 targeting pharmacological agents involved in inhibiting the progression of tumors have shown initial success in both clinical and pre-clinical experimental settings. Moreover, such agents improved angiogenesis, pro-inflammatory cytokine expression, and epithelial–mesenchymal transitions, upon TWEAK/Fn14 activation. This review provides an overview of the current understanding of the TWEAK–Fn14 signaling axis, its role in augmenting pathological characteristics of various diseases, and the existence of potential therapeutic targets for the development of novel pharmacological interventions.
KW - Pathological characteristics
KW - Pharmacological interventions
KW - Signaling pathway
KW - Therapeutic targets
KW - TWEAK/Fn14
UR - https://www.scopus.com/pages/publications/105024188229
U2 - 10.1016/j.genrep.2025.102403
DO - 10.1016/j.genrep.2025.102403
M3 - Artículo de revisión
AN - SCOPUS:105024188229
SN - 2452-0144
VL - 42
JO - Gene Reports
JF - Gene Reports
M1 - 102403
ER -