OncoTargets and Therapy (Feb 2020)
DEP Domain-Containing Protein 1B (DEPDC1B) Promotes Migration and Invasion in Pancreatic Cancer Through the Rac1/PAK1-LIMK1-Cofilin1 Signaling Pathway
Abstract
Shan Zhang, 1, 2,* Weiwei Shi, 1, 2,* Wei Hu, 3, 4,* Ding Ma, 1, 2 Dongliang Yan, 4 Kuanyong Yu, 4 Guang Zhang, 1, 2, 4 Yin Cao, 1, 2, 4 Junhua Wu, 2 Chunping Jiang, 1, 2, 4 Zhongxia Wang 1, 2, 4 1Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, People’s Republic of China; 2Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu 210093, People’s Republic of China; 3Department of Hepatobiliary Surgery, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, Jiangsu 222001, People’s Republic of China; 4Department of Hepatobiliary Surgery, Drum Tower Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhongxia Wang; Chunping Jiang 321 Zhongshan Road, Nanjing, Jiangsu 210008, People’s Republic of ChinaTel +86 15950451723; +86 13851818663Fax +86 25-83307115; +86 25-83307115Email [email protected]; [email protected]: With increasing incidence, pancreatic cancer (PC) is one of the most common digestive tract tumors. However, the prognosis of PC is particularly dismal due to the highly invasive and metastatic behavior of this deadly disease. DEP domain-containing protein 1B (DEPDC1B), which is overexpressed in multiple tumors, such as breast cancer, oral cancer and non-small cell lung cancer, plays a significant role in cell movement, cell cycle and cytoskeleton reorganization. However, the function of DEPDC1B in PC remains poorly understood.Methods: The function of DEPDC1B in the migration and invasion of PC was evaluated by wound healing and Transwell assays in vitro and PC-derived liver metastasis models in vivo. The molecular mechanisms of DEPDC1B were investigated through cell line establishment, Western blotting, qRT-PCR, immunoprecipitation, histological examination and immunohistochemistry analysis.Results: DEPDC1B was overexpressed in PC cell lines. DEPDC1B regulated cell migration and invasion. DEPDC1B regulated the Rac1/PAK1-LIMK1-cofilin1 signaling pathway by interacting with Rac1. Rac1 inhibition suppressed DEPDC1B-induced migration and invasion in PC in vitro and DEPDC1B-induced liver metastasis in vivo.Conclusion: DEPDC1B promoted cell migration and invasion by activating the Rac1/PAK1-LIMK1-cofilin1 signaling pathway, thus providing a potential therapeutic target against PC.Keywords: pancreatic cancer, DEP domain-containing protein 1B, migration, invasion, Rac1/PAK1-LIMK1-cofilin1 signaling
