Reduced kinase D‑interacting substrate of 220 kDa (Kidins220) in pancreatic cancer promotes EGFR/ERK signalling and disease progression

Cai,Shuo; Sun,Zhiwei; Sun,Ping-Hui; Gao,Xiangyu; Ji,Ke; Tian,Xiuyun; Ji,Jiafu; Hao,Chunyi; Soliman,Faris; Liu,Chang; Al‑Sarireh,Bilal; Griffiths,Paul; Hiscox,Stephen; Jiang,Wen G.; Ye,Lin

doi:10.3892/ijo.2021.5214

Reduced kinase D‑interacting substrate of 220 kDa (Kidins220) in pancreatic cancer promotes EGFR/ERK signalling and disease progression

Authors:
- Shuo Cai
- Zhiwei Sun
- Ping-Hui Sun
- Xiangyu Gao
- Ke Ji
- Xiuyun Tian
- Jiafu Ji
- Chunyi Hao
- Faris Soliman
- Chang Liu
- Bilal Al‑Sarireh
- Paul Griffiths
- Stephen Hiscox
- Wen G. Jiang
- Lin Ye
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Affiliations: Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff CF14 4XN, UK, Department of Hepato‑Pancreato‑Biliary Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China, Gastrointestinal Tumour Centre, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China, Department of Surgery, Morriston Hospital, ABM University Health Board, Swansea SA6 6NL, UK, Department of Pathology, Morriston Hospital, ABM University Health Board, Swansea SA6 6NL, UK, School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, UK
Published online on: May 6, 2021 https://doi.org/10.3892/ijo.2021.5214
Article Number: 34

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Abstract

Kidins220 is a transmembrane scaffold protein involved in several types of cancer. The aim of the present study was to examine the role of Kidins220 in tumorigenesis and disease progression of pancreatic cancer. The relevant signalling pathways including EGFR, EMT, and MMP were also investigated. The expression of Kidins220 was examined at the transcript and protein level. The Kidins220 knockdown cell model was established and its influence on cellular functions was determined. Involvement of Kidins220 in tumorigenesis and metastasis was examined in CD1 mice, respectively. The results showed that, reduced Kidin220 expression was associated with tumorigenesis, metastasis, and overall survival of pancreatic cancer. Knockdown of Kidins220 promoted proliferation, colony formation and tumorigenic capacity of pancreatic cancer cells in vitro and in vivo, respectively. Kidins220 regulated pancreatic cancer cell migration through the EGFR/AKT/ERK signalling pathway. Furthermore, enhanced EMT was observed in the pancreatic cancer cell lines with the knockdown of Kidins220, underlying EGFR regulation. Kidins220 also affected cell invasion via MMP1. A reduced expression of Kidins220 was observed in pancreatic cancer, which is associated with disease progression, distant metastasis and poor prognosis. The loss of Kidins220 in pancreatic cancer may contribute to disease progression through the upregulation of EGFR and downstream signalling.

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