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. 2021 Nov 15;16(11):e0259075.
doi: 10.1371/journal.pone.0259075. eCollection 2021.

Adaptor protein XB130 regulates the aggressiveness of cholangiocarcinoma

Pirawan Poosekeaw  1 , Chawalit Pairojkul  1 , Banchob Sripa  1 , Prakasit Sa Ngiamwibool  1 , Sitthichai Iamsaard  2 , Chadamas Sakonsinsiri  3   4 , Raynoo Thanan  3   4 , Piti Ungarreevittaya  1
Affiliations

Adaptor protein XB130 regulates the aggressiveness of cholangiocarcinoma

Pirawan Poosekeaw et al. PLoS One. .

Abstract

Cholangiocarcinoma (CCA) is a group of heterogenous malignancies arising from bile duct epithelium with distinct pathological features. Adaptor proteins have implicated in cell proliferation, migration, and invasion of different cancer cells. The objective of this study was to assess whether the adaptor protein XB130 (AFAP1L2) is a critical biological determinant of CCA outcome. XB130 expression levels were investigated in four CCA cell lines compared to an immortalized cholangiocyte cell line by Western blotting. Small interfering (si) RNA-mediated XB130 gene silencing was conducted to evaluate the effects of reduced XB130 expression on cell proliferation, migration, and invasion by MTT, transwell migration and cell invasion assay. The immunohistochemical quantification of XB130 levels were performed in surgically resected formalin-fixed, paraffin-embedded specimens obtained from 151 CCA patients. The relationship between XB130 expression and the clinicopathological parameters of CCA patients were analyzed. Our results showed that XB130 was highly expressed in KKU-213A cell line. Knockdown of XB130 using siRNA significantly decreased the proliferation, migration, and invasion properties of KKU-213A cells through the inhibition of PI3K/Akt pathway, suggesting that XB130 plays an important role in CCA progression. Moreover, elevated XB130 expression levels were positive relationship with lymphovascular space invasion (LVSI), intrahepatic type of CCA, high TNM staging (stage III, IV), high T classification (T3, T4), and lymph node metastasis. We provide the first evidence that the overexpression of XB130 is associated with tumorigenic properties of CCA cells, leading to CCA progression with aggressive clinical outcomes.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Western blot analysis of XB130 in MMNK1, KKU-100, KKU-213C, KKU-213A and KKU-023 cell lines, with β-actin as a loading control.
Fig 2
Fig 2. Effects of siXB130 on proliferation, motility and invasiveness of KKU-213A cell line.
A): The expressions of XB130 (130 kDa), E-cadherin (~135 kDa), vimentin (~54 kDa), Akt (~60 kDa), pAkt (~60 kDa) in siXB130 and scramble groups measured by western blotting, with β-actin as a loading control. B): MTT assays of the scramble and siXB130 treated cells. C): Hematoxylin-staining invasive cells from cell invasion assays of the scramble and siXB130 treated cells. D): Graphical represents numbers of invasive cells from cell invasion assays. E): Hematoxylin staining migrated cells from cell migration assays. F): Graphical represents numbers of migrating cells from cell migration assays. The asterisk (*) indicates statistical significance at P<0.05 and asterisks (***) indicates statistical significance at P < 0.001.
Fig 3
Fig 3. XB130 expression patterns in: A) normal bile duct; intensity = 48, B) hepatocyte; intensity = 72 and C) CCA intensity = 220 analyzed by IHC.
The scale bar equals 50 μm.
See this image and copyright information in PMC

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This study was financially supported by Invitation Research Fund from Faculty of Medicine, Khon Kaen University, Thailand to P.P. and P.U. (IN63122) and Thailand Research Fund to R.T. (RSA6280005).