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 ORCID: https://orcid.org/0000-0003-0105-2702, Jiang, Wen ORCID: https://orcid.org/0000-0002-3283-1111 and Ye, Lin ORCID: https://orcid.org/0000-0002-0303-2409 2021. Reduced kinase D‑interacting substrate of 220 kDa (Kidins220) in pancreatic cancer promotes EGFR/ERK signalling and disease progression. International Journal of Oncology 58 (6) , 34. 10.3892/ijo.2021.5214

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Pharmacy
Publisher:	Spandidos Publications
ISSN:	1019-6439
Date of First Compliant Deposit:	6 May 2021
Date of Acceptance:	13 April 2021
Last Modified:	06 Nov 2024 11:00
URI:	https://orca.cardiff.ac.uk/id/eprint/140957

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