2. Academic Validation
  3. WDR74 induces nuclear β-catenin accumulation and activates Wnt-responsive genes to promote lung cancer growth and metastasis

WDR74 induces nuclear β-catenin accumulation and activates Wnt-responsive genes to promote lung cancer growth and metastasis

  • Cancer Lett. 2020 Feb 28;471:103-115. doi: 10.1016/j.canlet.2019.12.011.
Yumei Li 1,  Fan Chen 1,  Weiyu Shen 1,  Bifei Li 1,  Rong Xiang 2,  Lijuan Qu 2,  Chen Zhang 1,  Gao Li 1,  Huanzhang Xie 1,  Vladimir L Katanaev 3,  Lee Jia 4
Affiliations

Affiliations

  • 1 Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University; Institute of Oceanography, Minjiang University, Fuzhou, Fujian, 350108, China.
  • 2 Department of Pathology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, 350025, China.
  • 3 Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University; Institute of Oceanography, Minjiang University, Fuzhou, Fujian, 350108, China; School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia; Translational Research Center in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Switzerland. Electronic address: Vladimir.Katanaev@unige.ch.
  • 4 Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University; Institute of Oceanography, Minjiang University, Fuzhou, Fujian, 350108, China. Electronic address: cmapcjia1234@163.com.
PMID: 31838084 DOI: 10.1016/j.canlet.2019.12.011
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.

Keywords

Lung cancer therapeutic target; WD repeat-containing protein 74; Wnt/β-catenin signaling cascade; β-Catenin translocation.

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