Adaptor protein XB130 regulates the aggressiveness of cholangiocarcinoma.

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 ada...

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Autores principales: Pirawan Poosekeaw, Chawalit Pairojkul, Banchob Sripa, Prakasit Sa Ngiamwibool, Sitthichai Iamsaard, Chadamas Sakonsinsiri, Raynoo Thanan, Piti Ungarreevittaya
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Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/fab656d034b54fc3b93e7cc92d225af7
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spelling oai:doaj.org-article:fab656d034b54fc3b93e7cc92d225af72021-12-02T20:13:12ZAdaptor protein XB130 regulates the aggressiveness of cholangiocarcinoma.1932-620310.1371/journal.pone.0259075https://doaj.org/article/fab656d034b54fc3b93e7cc92d225af72021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0259075https://doaj.org/toc/1932-6203Cholangiocarcinoma (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.Pirawan PoosekeawChawalit PairojkulBanchob SripaPrakasit Sa NgiamwiboolSitthichai IamsaardChadamas SakonsinsiriRaynoo ThananPiti UngarreevittayaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11, p e0259075 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Pirawan Poosekeaw
Chawalit Pairojkul
Banchob Sripa
Prakasit Sa Ngiamwibool
Sitthichai Iamsaard
Chadamas Sakonsinsiri
Raynoo Thanan
Piti Ungarreevittaya
Adaptor protein XB130 regulates the aggressiveness of cholangiocarcinoma.
description 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.
format article
author Pirawan Poosekeaw
Chawalit Pairojkul
Banchob Sripa
Prakasit Sa Ngiamwibool
Sitthichai Iamsaard
Chadamas Sakonsinsiri
Raynoo Thanan
Piti Ungarreevittaya
author_facet Pirawan Poosekeaw
Chawalit Pairojkul
Banchob Sripa
Prakasit Sa Ngiamwibool
Sitthichai Iamsaard
Chadamas Sakonsinsiri
Raynoo Thanan
Piti Ungarreevittaya
author_sort Pirawan Poosekeaw
title Adaptor protein XB130 regulates the aggressiveness of cholangiocarcinoma.
title_short Adaptor protein XB130 regulates the aggressiveness of cholangiocarcinoma.
title_full Adaptor protein XB130 regulates the aggressiveness of cholangiocarcinoma.
title_fullStr Adaptor protein XB130 regulates the aggressiveness of cholangiocarcinoma.
title_full_unstemmed Adaptor protein XB130 regulates the aggressiveness of cholangiocarcinoma.
title_sort adaptor protein xb130 regulates the aggressiveness of cholangiocarcinoma.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/fab656d034b54fc3b93e7cc92d225af7
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