The effects and mechanisms of SLC34A2 on maintaining stem cell-like phenotypes in CD147 breast cancer stem cells

The cancer stem cell (CSC) hypothesis has gained significant recognition in describing tumorigenesis. Identification of the factors critical to development of breast cancer stem cells (BCSCs) may provide insight into the improvement of effective therapies against breast cancer. In this study, we aim...

Full description

Saved in:
Bibliographic Details
Main Authors: Yonggang Lv, Ting Wang, Jing Fan, Zhenzhen Zhang, Juliang Zhang, Cheng Xu, Yongping Li, Ge Zhao, Chenyang He, Huimin Meng, Hua Yang, Zhen Wang, Jiayun Liu, Jianghao Chen, Ling Wang
Format: Article
Language:English
Published: SAGE Publishing 2017-04-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317695927
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849417526758342656
author Yonggang Lv
Ting Wang
Jing Fan
Zhenzhen Zhang
Juliang Zhang
Cheng Xu
Yongping Li
Ge Zhao
Chenyang He
Huimin Meng
Hua Yang
Zhen Wang
Jiayun Liu
Jianghao Chen
Ling Wang
author_facet Yonggang Lv
Ting Wang
Jing Fan
Zhenzhen Zhang
Juliang Zhang
Cheng Xu
Yongping Li
Ge Zhao
Chenyang He
Huimin Meng
Hua Yang
Zhen Wang
Jiayun Liu
Jianghao Chen
Ling Wang
author_sort Yonggang Lv
collection DOAJ
description The cancer stem cell (CSC) hypothesis has gained significant recognition in describing tumorigenesis. Identification of the factors critical to development of breast cancer stem cells (BCSCs) may provide insight into the improvement of effective therapies against breast cancer. In this study, we aim to investigate the biological function of SLC34A2 in affecting the stem cell-like phenotypes in BCSCs and its underlying mechanisms. We demonstrated that CD147 + cells from breast cancer tissue samples and cell lines possessed BCSC-like features, including the ability of self-renewal in vitro, differentiation, and tumorigenic potential in vivo. Flow cytometry analysis showed the presence of a variable fraction of CD147 + cells in 9 of 10 tumor samples. Significantly, SLC34A2 expression in CD147 + BCSCs was enhanced compared with that in differentiated adherent progeny of CD147 + BCSCs and adherently cultured cell line cells. In breast cancer patient cohorts, SLC34A2 expression was found increased in 9 of 10 tumor samples. By using lentiviral-based approach, si-SLC34A2-transduced CD147 + BCSCs showed decreased ability of sphere formation, cell viability in vitro, and tumorigenicity in vivo, which suggested the essential role of SLC34A2 in CD147 + BCSCs. Furthermore, PI3K/AKT pathway and SOX2 were found necessary to maintain the stemness of CD147 + BCSCs by using LY294002 or lentiviral-si-SOX2. Finally, we indicated that SLC34A2 could regulate SOX2 to maintain the stem cell–like features in CD147 + BCSCs through PI3K/AKT pathway. Therefore, our report identifies a novel role of SLC34A2 in BCSCs’ state regulation and establishes a rationale for targeting the SLC34A2/PI3K/AKT/SOX2 signaling pathway for breast cancer therapy.
format Article
id doaj-art-1e76535c446844ec8651c4cb466f14bf
institution Kabale University
issn 1423-0380
language English
publishDate 2017-04-01
publisher SAGE Publishing
record_format Article
series Tumor Biology
spelling doaj-art-1e76535c446844ec8651c4cb466f14bf2025-08-20T03:32:47ZengSAGE PublishingTumor Biology1423-03802017-04-013910.1177/1010428317695927The effects and mechanisms of SLC34A2 on maintaining stem cell-like phenotypes in CD147 breast cancer stem cellsYonggang Lv0Ting Wang1Jing Fan2Zhenzhen Zhang3Juliang Zhang4Cheng Xu5Yongping Li6Ge Zhao7Chenyang He8Huimin Meng9Hua Yang10Zhen Wang11Jiayun Liu12Jianghao Chen13Ling Wang14Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of ChinaDepartment of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of ChinaDepartment of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of ChinaBiotecan Medical Diagnostics Co. Ltd., Zhangjiang Center for Translational Medicine, Shanghai, People’s Republic of ChinaDepartment of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of ChinaBiotecan Medical Diagnostics Co. Ltd., Zhangjiang Center for Translational Medicine, Shanghai, People’s Republic of ChinaDepartment of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of ChinaDepartment of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of ChinaDepartment of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of ChinaDepartment of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of ChinaDepartment of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of ChinaDepartment of Orthopaedic, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of ChinaInstitute of Clinical Laboratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi’ an, People’s Republic of ChinaDepartment of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of ChinaDepartment of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of ChinaThe cancer stem cell (CSC) hypothesis has gained significant recognition in describing tumorigenesis. Identification of the factors critical to development of breast cancer stem cells (BCSCs) may provide insight into the improvement of effective therapies against breast cancer. In this study, we aim to investigate the biological function of SLC34A2 in affecting the stem cell-like phenotypes in BCSCs and its underlying mechanisms. We demonstrated that CD147 + cells from breast cancer tissue samples and cell lines possessed BCSC-like features, including the ability of self-renewal in vitro, differentiation, and tumorigenic potential in vivo. Flow cytometry analysis showed the presence of a variable fraction of CD147 + cells in 9 of 10 tumor samples. Significantly, SLC34A2 expression in CD147 + BCSCs was enhanced compared with that in differentiated adherent progeny of CD147 + BCSCs and adherently cultured cell line cells. In breast cancer patient cohorts, SLC34A2 expression was found increased in 9 of 10 tumor samples. By using lentiviral-based approach, si-SLC34A2-transduced CD147 + BCSCs showed decreased ability of sphere formation, cell viability in vitro, and tumorigenicity in vivo, which suggested the essential role of SLC34A2 in CD147 + BCSCs. Furthermore, PI3K/AKT pathway and SOX2 were found necessary to maintain the stemness of CD147 + BCSCs by using LY294002 or lentiviral-si-SOX2. Finally, we indicated that SLC34A2 could regulate SOX2 to maintain the stem cell–like features in CD147 + BCSCs through PI3K/AKT pathway. Therefore, our report identifies a novel role of SLC34A2 in BCSCs’ state regulation and establishes a rationale for targeting the SLC34A2/PI3K/AKT/SOX2 signaling pathway for breast cancer therapy.https://doi.org/10.1177/1010428317695927
spellingShingle Yonggang Lv
Ting Wang
Jing Fan
Zhenzhen Zhang
Juliang Zhang
Cheng Xu
Yongping Li
Ge Zhao
Chenyang He
Huimin Meng
Hua Yang
Zhen Wang
Jiayun Liu
Jianghao Chen
Ling Wang
The effects and mechanisms of SLC34A2 on maintaining stem cell-like phenotypes in CD147 breast cancer stem cells
Tumor Biology
title The effects and mechanisms of SLC34A2 on maintaining stem cell-like phenotypes in CD147 breast cancer stem cells
title_full The effects and mechanisms of SLC34A2 on maintaining stem cell-like phenotypes in CD147 breast cancer stem cells
title_fullStr The effects and mechanisms of SLC34A2 on maintaining stem cell-like phenotypes in CD147 breast cancer stem cells
title_full_unstemmed The effects and mechanisms of SLC34A2 on maintaining stem cell-like phenotypes in CD147 breast cancer stem cells
title_short The effects and mechanisms of SLC34A2 on maintaining stem cell-like phenotypes in CD147 breast cancer stem cells
title_sort effects and mechanisms of slc34a2 on maintaining stem cell like phenotypes in cd147 breast cancer stem cells
url https://doi.org/10.1177/1010428317695927
work_keys_str_mv AT yongganglv theeffectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT tingwang theeffectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT jingfan theeffectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT zhenzhenzhang theeffectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT juliangzhang theeffectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT chengxu theeffectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT yongpingli theeffectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT gezhao theeffectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT chenyanghe theeffectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT huiminmeng theeffectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT huayang theeffectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT zhenwang theeffectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT jiayunliu theeffectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT jianghaochen theeffectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT lingwang theeffectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT yongganglv effectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT tingwang effectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT jingfan effectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT zhenzhenzhang effectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT juliangzhang effectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT chengxu effectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT yongpingli effectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT gezhao effectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT chenyanghe effectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT huiminmeng effectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT huayang effectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT zhenwang effectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT jiayunliu effectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT jianghaochen effectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells
AT lingwang effectsandmechanismsofslc34a2onmaintainingstemcelllikephenotypesincd147breastcancerstemcells