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WDR74 induces nuclear β-catenin accumulation and activates Wnt-responsive genes to promote lung cancer growth and metastasis.
- Source :
-
Cancer Letters . Feb2020, Vol. 471, p103-115. 13p. - Publication Year :
- 2020
-
Abstract
- Lung cancer has been notorious for its lack of advance in clinical therapy, urging for effective therapeutic targets. WD repeat-containing protein 74 (WDR74) has previously been implicated in tumorigenesis, but its mechanistic functions remain not well understood. Herein, WDR74 expression was observed to be increased upon lung cancer progression from healthy normal tissues to the primary cancer and further to the metastatic cancer. Through gain- and loss-of-function approaches, we found that WDR74 regulated lung cancer cell proliferation, cell cycle progression, chemoresistance and cell aggressiveness in vitro. Moreover, a xenograft mouse model disclosed that WDR74 knockout inhibited lung cancer growth and metastasis, whereas WDR74 overexpression reciprocally enhanced these characteristics. Mechanistically, WDR74 promoted nuclear β-catenin accumulation and drove downstream Wnt-responsive genes, thus revealing that WDR74 activated the Wnt/β-catenin signaling pathway. Collectively, WDR74 inducing nuclear β-catenin accumulation and driving the downstream Wnt-responsive genes expression facilitates lung cancer growth and metastasis. WDR74 can serve as a candidate target for the prevention and treatment of lung cancer in clinic. [ABSTRACT FROM AUTHOR]
- Subjects :
- *WNT genes
*LUNG cancer
*TUMOR growth
*METASTASIS
*CANCER cell proliferation
*CANCER invasiveness
*PROTEIN metabolism
*PROTEINS
*DISEASE progression
*RESEARCH
*XENOGRAFTS
*DOXORUBICIN
*ANIMAL experimentation
*RESEARCH methodology
*CYTOSKELETAL proteins
*LUNG tumors
*CELL physiology
*EVALUATION research
*MEDICAL cooperation
*CELLULAR signal transduction
*CELL cycle
*COMPARATIVE studies
*GENES
*CELL lines
*PHOSPHORYLATION
*DRUG resistance in cancer cells
*MICE
*PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 03043835
- Volume :
- 471
- Database :
- Academic Search Index
- Journal :
- Cancer Letters
- Publication Type :
- Academic Journal
- Accession number :
- 140919388
- Full Text :
- https://doi.org/10.1016/j.canlet.2019.12.011