Results 61 to 70 of about 736,089 (295)

Cytoplasmic p21 promotes stemness of colon cancer cells via activation of the NFκB pathway

Molecular Oncology, EarlyView.
Cytoplasmic p21 promotes colorectal cancer stem cell (CSC) features by destabilizing the NFκB–IκB complex, activating NFκB signaling, and upregulating BCL‐xL and COX2. In contrast to nuclear p21, cytoplasmic p21 enhances spheroid formation and stemness transcription factor CD133.
Arnatchai Maiuthed, Kerstin Huebner, Katharina Erlenbach‐Wuensch, Chuanpit Hampel, Daniela Thalheim, Adriana Vial‐Roehe, Bodee Nutho, Susanne Merkel, Arndt Hartmann, Pithi Chanvorachote, Regine Schneider‐Stock   +10 more
wiley   +1 more source

Class IIa HDACs forced degradation allows resensitization of oxaliplatin‐resistant FBXW7‐mutated colorectal cancer

Molecular Oncology, EarlyView.
HDAC4 is degraded by the E3 ligase FBXW7. In colorectal cancer, FBXW7 mutations prevent HDAC4 degradation, leading to oxaliplatin resistance. Forced degradation of HDAC4 using a PROTAC compound restores drug sensitivity by resetting the super‐enhancer landscape, reprogramming the epigenetic state of FBXW7‐mutated cells to resemble oxaliplatin ...
Vanessa Tolotto, Nicolò Gualandi, Ylenia Cortolezzis, Raffaella Picco, Monica Colitti, Francesca D'Este, Mariachiara Gani, Wayne W. Hancock, Giovanni Terrosu, Cristina Degrassi, Francesca Agostini, Claudio Brancolini, Luigi E. Xodo, Eros Di Giorgio   +13 more
wiley   +1 more source

Dual targeting of RET and SRC synergizes in RET fusion‐positive cancer cells

Molecular Oncology, EarlyView.
Despite the strong activity of selective RET tyrosine kinase inhibitors (TKIs), resistance of RET fusion‐positive (RET+) lung cancer and thyroid cancer frequently occurs and is mainly driven by RET‐independent bypass mechanisms. Son et al. show that SRC TKIs significantly inhibit PAK and AKT survival signaling and enhance the efficacy of RET TKIs in ...
Juhyeon Son, Lily L. Remsing Rix, Bin Fang, Eric A. Welsh, Nicole V. Bremer, Valentina Foglizzo, Paola Roa, Nickole Sigcha‐Coello, Yi Liao, Eric B. Haura, Alexander Drilon, John M. Koomen, Emiliano Cocco, Uwe Rix   +13 more
wiley   +1 more source

Effective therapeutic targeting of CTNNB1‐mutant hepatoblastoma with WNTinib

Molecular Oncology, EarlyView.
WNTinib, a Wnt/CTNNB1 inhibitor, was tested in hepatoblastoma (HB) experimental models. It delayed tumor growth and improved survival in CTNNB1‐mutant in vivo models. In organoids, WNTinib outperformed cisplatin and showed enhanced efficacy in combination therapy, supporting its potential as a targeted treatment for CTNNB1‐mutated HB.
Ugne Balaseviciute, Júlia Huguet‐Pradell, Jordi Abril‐Fornaguera, Albert Gris‐Oliver, Alex Rialdi, Elisa Fernández‐Martínez, Carla Montironi, Vanessa Del Pozo, Peter Houghton, Laura Zanatto, Agavni Mesropian, Ieva Keraite, Swan Thung, Carolina Armengol, Pau Sancho‐Bru, Ernesto Guccione, Roser Pinyol, Josep M. Llovet   +17 more
wiley   +1 more source

ATF4‐mediated stress response as a therapeutic vulnerability in chordoma

Molecular Oncology, EarlyView.
We screened 5 chordoma cell lines against 100+ inhibitors of epigenetic and metabolic pathways and kinases and identified halofuginone, a tRNA synthetase inhibitor. Mechanistically halofuginone induces an integrated stress response, with eIF2alpha phosphorylation, activation of ATF4 and its target genes CHOP, ASNS, INHBE leading to cell death ...
Lucia Cottone, James Dunford, Eleanor Calcutt, Vicki Gamble, Filiz Senbabaoglu Aksu, Lorena Ligammari, Georgina Wherry, Giorgia Gaeta, John C. Christianson, Adrienne M. Flanagan, Udo Oppermann, Adam P. Cribbs   +11 more
wiley   +1 more source

Cell surface interactome analysis identifies TSPAN4 as a negative regulator of PD‐L1 in melanoma

Molecular Oncology, EarlyView.
Using cell surface proximity biotinylation, we identified tetraspanin TSPAN4 within the PD‐L1 interactome of melanoma cells. TSPAN4 negatively regulates PD‐L1 expression and lateral mobility by limiting its interaction with CMTM6 and promoting PD‐L1 degradation.
Guus A. Franken, Andrea Abel Gutierrez, Imke van Rossum, Cornelia G. Spruijt, Michiel Vermeulen, Guido van Mierlo, Blanca Scheijen, Annemiek B. van Spriel   +7 more
wiley   +1 more source

Therapeutic strategies for MMAE‐resistant bladder cancer through DPP4 inhibition

Molecular Oncology, EarlyView.
We established monomethyl auristatin E (MMAE)‐resistant bladder cancer (BC) cell lines by exposure to progressively increasing concentrations of MMAE in vitro. RNA sequencing showed DPP4 expression was increased in MMAE‐resistant BC cells. Both si‐DPP4 and the DPP4 inhibitor sitagliptin suppressed the viability of MMAE‐resistant BC cells.
Gang Li, Shuichi Tatarano, Hirofumi Yoshino, Saeki Saito, Mitsuhiko Tominaga, Junya Arima, Ikumi Fukuda, Takashi Sakaguchi, Ryosuke Matsushita, Yasutoshi Yamada, Hideki Enokida   +10 more
wiley   +1 more source

Peroxidasin enables melanoma immune escape by inhibiting natural killer cell cytotoxicity

Molecular Oncology, EarlyView.
Peroxidasin (PXDN) is secreted by melanoma cells and binds the NK cell receptor NKG2D, thereby suppressing NK cell activation and cytotoxicity. PXDN depletion restores NKG2D signaling and enables effective NK cell–mediated melanoma killing. These findings identify PXDN as a previously unrecognized immune evasion factor and a potential target to improve
Hsu‐Min Sung, David Bickel, Lena C. M. Krause, Daria Ezeriņa, Christian Ickes, Julian Wojtachnia, Christine S. Gibhardt, Magdalena Shumanska, Khadija Wahni, Andrea Paluschkiwitz, Julia Malo Pueyo, Ekaterina Baranova, Wim Vranken, Hedwig Stanisz, Ioana Stejerean‐Todoran, Michael P. Schön, Joris Messens, Ivan Bogeski   +17 more
wiley   +1 more source

Redox regulation meets metabolism: targeting PRDX2 to prevent hepatocellular carcinoma

Molecular Oncology, EarlyView.
PRDX2 acts as a central redox hub linking metabolic dysfunction‐associated steatohepatitis (MASH) to hepatocellular carcinoma (HCC). In normal hepatocytes, PRDX2 maintains redox balance and metabolic homeostasis under oxidative stress. In contrast, during malignant transformation, PRDX2 promotes oncogenic signaling, stemness, and tumor initiation ...
Naroa Goikoetxea‐Usandizaga, María Luz Martinez‐Chantar, Carolina Conter   +2 more
wiley   +1 more source

Dammarenediol II enhances etoposide‐induced apoptosis by targeting O‐GlcNAc transferase and Akt/GSK3β/mTOR signaling in liver cancer

Molecular Oncology, EarlyView.
Etoposide induces DNA damage, activating p53‐dependent apoptosis via caspase‐3/7, which cleaves PARP1. Dammarenediol II enhances this apoptotic pathway by suppressing O‐GlcNAc transferase activity, further decreasing O‐GlcNAcylation. The reduction in O‐GlcNAc levels boosts p53‐driven apoptosis and influences the Akt/GSK3β/mTOR signaling pathway ...
Jaehoon Lee, Byung‐Cheol Han, Gi‐Bang Koo, Jihye Park, Mijin Kwon, Young Bin Park, Jae‐Mun Choi, Seung‐Ho Lee, Sangho Roh   +8 more
wiley   +1 more source