SRC‑like adaptor protein negatively regulates Wnt signaling in intrahepatic cholangiocarcinoma

Wang,Yong; He,Xinxin; Wei,Yangnian; Liu,Ling; Wang,Wen; Li,Nianfeng

doi:10.3892/ol.2019.9901

SRC‑like adaptor protein negatively regulates Wnt signaling in intrahepatic cholangiocarcinoma

Authors:
- Yong Wang
- Xinxin He
- Yangnian Wei
- Ling Liu
- Wen Wang
- Nianfeng Li
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Affiliations: Department of Hepatobiliary and Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: January 8, 2019 https://doi.org/10.3892/ol.2019.9901
Pages: 2745-2753
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Currently, the molecular mechanisms underlying intrahepatic cholangiocarcinoma (IHCC) are poorly understood. In the present study, the focus was primarily on SRC‑like adaptor protein (SLAP), an adaptor protein, which is aberrantly expressed in various cancer types. To the best of our knowledge, the present study was the first to demonstrate that SLAP was decreased in IHCC tissues and cells, compared with controls. Further study indicated that SLAP overexpression suppressed IHCC cell proliferation and induced cell cycle arrest, indicating the tumor suppressor role of SLAP in IHCC progression. To demonstrate the effects of SLAP on Wnt signaling, the β‑catenin/T cell factor transcription reporter assay was conducted. Compared with the negative adenovirus vector control (Ad‑NC), overexpression of SLAP reduced TOPflash activity, and no changes in FOPflash activity were identified. Furthermore, the expression levels of Wnt target genes, including β‑catenin, c‑Myc, cluster of differentiation 44, Slug, Vimentin and matrix metallopeptidase‑9, were reduced in RBE and Huh28 cells overexpressing SLAP. Additionally, the effects of SLAP on IHCC cell invasion and migration were determined. Compared with the Ad‑NC control, the migration and invasion capacity was reduced following overexpression of SLAP in RBE and Huh28 cells. In summary, reduced SLAP expression may enhance IHCC malignant progression by activating Wnt signaling.

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