Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal Cancer

Salvador homolog-1 (SAV1) is a component of the Hippo pathway that regulates tissue growth and homeostasis by affecting diverse cell processes, including apoptosis, cell division, and differentiation. The aberrant expression of Hippo pathway components has been observed in various human cancers. Thi...

Full description

Bibliographic Details
Main Authors: Anna Ewa Kowalczyk, Bartlomiej Emil Krazinski, Aleksandra Piotrowska, Jedrzej Grzegrzolka, Janusz Godlewski, Piotr Dziegiel, Zbigniew Kmiec
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/15/24/5771
_version_ 1797381759776587776
author Anna Ewa Kowalczyk
Bartlomiej Emil Krazinski
Aleksandra Piotrowska
Jedrzej Grzegrzolka
Janusz Godlewski
Piotr Dziegiel
Zbigniew Kmiec
author_facet Anna Ewa Kowalczyk
Bartlomiej Emil Krazinski
Aleksandra Piotrowska
Jedrzej Grzegrzolka
Janusz Godlewski
Piotr Dziegiel
Zbigniew Kmiec
author_sort Anna Ewa Kowalczyk
collection DOAJ
description Salvador homolog-1 (SAV1) is a component of the Hippo pathway that regulates tissue growth and homeostasis by affecting diverse cell processes, including apoptosis, cell division, and differentiation. The aberrant expression of Hippo pathway components has been observed in various human cancers. This study aimed to examine the expression level of the <i>SAV1</i> gene in colorectal cancer (CRC) and its prognostic value and associations with tumor progression. We obtained matched pairs of tumor tissue and non-cancerous mucosa of the large intestine from 94 CRC patients as well as 40 colon biopsies of healthy subjects collected during screening colonoscopy. The tissue samples and CRC cell lines were quantified for <i>SAV1</i> mRNA levels using the quantitative polymerase chain reaction method, while SAV1 protein expression was estimated in the paired tissues of CRC patients using immunohistochemistry. The average level of <i>SAV1</i> mRNA was decreased in 93.6% of the tumor tissues compared to the corresponding non-cancerous tissues and biopsies of healthy colon mucosa. A downregulated expression of <i>SAV1</i> mRNA was also noted in the CRC cell lines. Although the average SAV1 immunoreactivity was increased in the CRC samples compared to the non-cancerous tissues, a decreased immunoreactivity of the SAV1 protein in the tumor specimens was associated with lymph node involvement and higher TNM disease stage and histological grade. The results of our study suggest that the impaired expression of SAV1 is involved in CRC progression.
first_indexed 2024-03-08T20:56:07Z
format Article
id doaj.art-d0ab819c15d94173b6dfd100ae3dba99
institution Directory Open Access Journal
issn 2072-6694
language English
last_indexed 2024-03-08T20:56:07Z
publishDate 2023-12-01
publisher MDPI AG
record_format Article
series Cancers
spelling doaj.art-d0ab819c15d94173b6dfd100ae3dba992023-12-22T13:58:49ZengMDPI AGCancers2072-66942023-12-011524577110.3390/cancers15245771Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal CancerAnna Ewa Kowalczyk0Bartlomiej Emil Krazinski1Aleksandra Piotrowska2Jedrzej Grzegrzolka3Janusz Godlewski4Piotr Dziegiel5Zbigniew Kmiec6Department of Human Histology and Embryology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, PolandDepartment of Human Histology and Embryology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, PolandDivision of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, PolandDivision of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, PolandDepartment of Human Histology and Embryology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, PolandDivision of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, PolandDepartment of Histology, Medical University of Gdansk, 80-210 Gdansk, PolandSalvador homolog-1 (SAV1) is a component of the Hippo pathway that regulates tissue growth and homeostasis by affecting diverse cell processes, including apoptosis, cell division, and differentiation. The aberrant expression of Hippo pathway components has been observed in various human cancers. This study aimed to examine the expression level of the <i>SAV1</i> gene in colorectal cancer (CRC) and its prognostic value and associations with tumor progression. We obtained matched pairs of tumor tissue and non-cancerous mucosa of the large intestine from 94 CRC patients as well as 40 colon biopsies of healthy subjects collected during screening colonoscopy. The tissue samples and CRC cell lines were quantified for <i>SAV1</i> mRNA levels using the quantitative polymerase chain reaction method, while SAV1 protein expression was estimated in the paired tissues of CRC patients using immunohistochemistry. The average level of <i>SAV1</i> mRNA was decreased in 93.6% of the tumor tissues compared to the corresponding non-cancerous tissues and biopsies of healthy colon mucosa. A downregulated expression of <i>SAV1</i> mRNA was also noted in the CRC cell lines. Although the average SAV1 immunoreactivity was increased in the CRC samples compared to the non-cancerous tissues, a decreased immunoreactivity of the SAV1 protein in the tumor specimens was associated with lymph node involvement and higher TNM disease stage and histological grade. The results of our study suggest that the impaired expression of SAV1 is involved in CRC progression.https://www.mdpi.com/2072-6694/15/24/5771SAV1colorectal cancerclinicopathological parametersHippo pathway
spellingShingle Anna Ewa Kowalczyk
Bartlomiej Emil Krazinski
Aleksandra Piotrowska
Jedrzej Grzegrzolka
Janusz Godlewski
Piotr Dziegiel
Zbigniew Kmiec
Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal Cancer
Cancers
SAV1
colorectal cancer
clinicopathological parameters
Hippo pathway
title Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal Cancer
title_full Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal Cancer
title_fullStr Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal Cancer
title_full_unstemmed Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal Cancer
title_short Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal Cancer
title_sort impaired expression of the salvador homolog 1 gene is associated with the development and progression of colorectal cancer
topic SAV1
colorectal cancer
clinicopathological parameters
Hippo pathway
url https://www.mdpi.com/2072-6694/15/24/5771
work_keys_str_mv AT annaewakowalczyk impairedexpressionofthesalvadorhomolog1geneisassociatedwiththedevelopmentandprogressionofcolorectalcancer
AT bartlomiejemilkrazinski impairedexpressionofthesalvadorhomolog1geneisassociatedwiththedevelopmentandprogressionofcolorectalcancer
AT aleksandrapiotrowska impairedexpressionofthesalvadorhomolog1geneisassociatedwiththedevelopmentandprogressionofcolorectalcancer
AT jedrzejgrzegrzolka impairedexpressionofthesalvadorhomolog1geneisassociatedwiththedevelopmentandprogressionofcolorectalcancer
AT januszgodlewski impairedexpressionofthesalvadorhomolog1geneisassociatedwiththedevelopmentandprogressionofcolorectalcancer
AT piotrdziegiel impairedexpressionofthesalvadorhomolog1geneisassociatedwiththedevelopmentandprogressionofcolorectalcancer
AT zbigniewkmiec impairedexpressionofthesalvadorhomolog1geneisassociatedwiththedevelopmentandprogressionofcolorectalcancer