The clinical and biological implications of the focal adhesion kinase pathway in ShenLingLan mediated suppression of cellular migration of ovarian cancer cells

Owen, Sioned, Ruge, Fiona, Gao, YuNong, Yang, Ying, Hou, Jianli, Chen, Jian, Lane, Jane ORCID: https://orcid.org/0000-0002-1926-4909, Gao, Yong, Wang, HongTao, Wu, Yiling and Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111 2017. The clinical and biological implications of the focal adhesion kinase pathway in ShenLingLan mediated suppression of cellular migration of ovarian cancer cells. Journal of Cancer Research & Therapy 5 , pp. 24-31. 10.14312/2052-4994.2017-5

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Abstract

The incidence of ovarian cancer in the UK has increased by almost twenty percent since the 1970’s and the majority of cases are not diagnosed until the late stages, when metastasis is more likely to have occurred. Focal Adhesion Kinase (FAK) is one of the key protein complexes which is integral to cell migration and has been linked to a variety of solid tumours. ShenLingLan (SLDM) is a traditional herbal medicine which has been formulated for the treatment of solid tumours. This study aimed to establish the impact of SLDM on FAK in ovarian cancer cells in vitro and transcript levels of FAK in an ovarian cancer cohort. FAK and paxillin phosphorylation events stimulated by SLDM treatment were identified using a Kinexus™ antibody based protein array. The impact of SLDM on cell attachment and migration was evaluated using Electric cell-substrate impedance sensing (ECIS), whilst the changes in focal adhesion complex localisation were assessed using immunofluorescence. In an ovarian cancer cohort, differences in FAK and paxillin transcript levels were assessed against key clinical parameters such as differentiation, stage and survival outcome. SLDM treatment of ovarian cancer cells in vitro resulted in the suppression of FAK and paxillin phosphorylation at several sites, which appeared to manifest as decreased cellular attachment and migration in a range of immortalised ovarian cancer cells. Increased FAK and paxillin transcript copies were observed in high grade and poorly differentiated ovarian tumours as well as in tumours from patients with ovarian cancer related incidence. SLDM has a profound effect on the migratory and adhesive properties of ovarian cancer cells, potentially via inhibitory effects on the activation of the FAK pathway, which is aberrant in clinical ovarian cancers.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	ShenLingLan; ovarian cancer; cell migration; FAK; paxillin; protein array
Publisher:	Noble Research
ISSN:	2052-4994
Funders:	the Welsh National Research Network/ Ser Cymru and Cancer Research Wales
Date of First Compliant Deposit:	19 June 2017
Date of Acceptance:	20 May 2017
Last Modified:	20 Jan 2024 14:42
URI:	https://orca.cardiff.ac.uk/id/eprint/101540

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