Abstract:
Background:Extracellular ATP (eATP) was shown to induce epithelial-mesenchymal transition (EMT), a very important early process in metastasis, in cancer cells via purinergic receptor signaling. However, the exact induction mechanisms are far from fully known. We previously described that eATP is internalized by cancer cells in vitro and in vivo by macropinocytosis in human non-small cell lung cancer A549 and other cancer cells, drastically elevates intracellular ATP levels, enhances cell proliferation and resistance to anticancer drugs. In this study, we tested the hypothesis that eATP and macropinocytosis-internalized eATP also induces EMT and other early steps of metastasis. Methods:Floating cells, fencing, and transwell assays were used to show that ATP induces cell detachment, new colony formation, migration and invasion in human A549 and other lung cancer cells. Western blots were used to detect ATP-induced changes in EMT-related proteins; Confocal microscopy was used to demonstrate ATP-induced metastasis-related cell morphological changes. Inhibitors and siRNA knockdowns were used to determine P2X7's involvement in the ATP-induced EMT. CRISPR-Cas9 knockout of the SNX5 gene was used to identify macropinocytosis' roles in EMT and cancer cell growth both in vitro and in vivo. Student t-test and one-way ANOVA were used to determine statistical significance, P < 0.05 was considered significant. Results:eATP potently induces expression of matrix metallopeptidases (MMPs), and detachment, EMT, migration, and invasion of lung cancer cells. The induction was independent of TGF-β and semi-independent of P2X7 activation. eATP performs these functions not only extracellularly, but also intracellularly after being macropinocytically internalized to further enhance P2X7-mediated EMT, filopodia formation and other early steps of metastasis. The knockout of macropinocytosis-associated SNX5 gene significantly reduces macropinocytosis, slows down tumor growth, and changes tumor morphology in nude mice. Conclusions:Collectively, these results show that eATP's functions in these processes not only from outside of cancer cells but also inside after being macropinocytotically internalized. These findings shed light on eATP's initiator and effector roles in almost every step in early metastasis, which calls for rethinking and rebalancing energy equations of intracellular biochemical reactions and the Warburg effect, and identifies eATP and macropinocytosis as novel targets for potentially slowing down EMT and preventing metastasis.
journal_name
Cancer Cell Intjournal_title
Cancer cell internationalauthors
Cao Y,Wang X,Li Y,Evers M,Zhang H,Chen Xdoi
10.1186/s12935-019-0973-0subject
Has Abstractpub_date
2019-10-01 00:00:00pages
254issn
1475-2867pii
973journal_volume
19pub_type
杂志文章abstract::Circular RNAs (circRNAs) are small non-coding RNAs with a unique ring structure and play important roles as gene regulators. Disturbed expressions of circRNAs is closely related to varieties of pathological processes. The roles of circRNAs in cancers have gained increasing concerns. The communications between the canc...
journal_title:Cancer cell international
pub_type: 杂志文章,评审
doi:10.1186/s12935-020-01301-z
更新日期:2020-06-03 00:00:00
abstract:Background:Breast cancer is one of the most common malignancy among females from the worldwide cancer incidence statistics. Peroxisome gamma coactivator-1β (PGC-1β) has long been identified to be involved in this type of tumorigenesis. However, the mechanisms of PGC-1β in human breast cancer have not been fully underst...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-0810-5
更新日期:2019-04-11 00:00:00
abstract:BACKGROUND:Endometrial cancer is an invasive gynecological cancer prevalent in the world. The pathogenesis of endometrial cancer is related to multiple levels of regulation, referring to oestrogen, tumor-suppressor gene (e.g. PTEN) or microRNAs (e.g. miR-23a and miR-29b). Metapristone is a hormone-related drug, which i...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01682-1
更新日期:2021-01-07 00:00:00
abstract::[This retracts the article DOI: 10.1186/s12935-015-0237-6.]. ...
journal_title:Cancer cell international
pub_type: 撤回出版物
doi:10.1186/s12935-016-0359-5
更新日期:2016-11-04 00:00:00
abstract::Prostate cancer is a gland tumor in the male reproductive system. It is a multifaceted and genomically complex disease. Transmembrane protease, serine 2 and v-ets erythroblastosis virus E26 homolog (TMPRSS2-ERG) gene fusions are the common molecular signature of prostate cancer. Although tremendous advances have been ...
journal_title:Cancer cell international
pub_type: 杂志文章,评审
doi:10.1186/1475-2867-14-34
更新日期:2014-04-17 00:00:00
abstract:Background:Newly identified lncRNA zinc finger protein, FOG family member 2 antisense RNA 1 (ZFPM2-AS1) is identified as an oncogenic gene. However, the role of ZFPM2-AS1 in small cell lung cancer (SCLC) is poorly comprehended. Methods:The expression of genes in SCLC tissues and cells was measured by qRT-PCR. Colony f...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-1157-7
更新日期:2020-04-03 00:00:00
abstract:BACKGROUND:We previously observed that the TGFbeta-Par6 pathway mediates loss of polarity and apoptosis in NMuMG cells. Here we investigate the contribution of Par6 versus TGFbeta receptor I activation to TGFbeta-induced apoptosis in association with changes in apico-basal polarity. We focus on the effect of Par6 activ...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-14-19
更新日期:2014-03-01 00:00:00
abstract:Background:Melanoma is the most aggressive type of skin cancer with high mortality rate and poor prognosis. lncRNA MEG3, a tumor suppressor, is closely related to the development of various cancers. However, the role of lncRNA MEG3 in melanoma has seldom been studied. Methods:RT-PCR was used to examine the expressions...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-1087-4
更新日期:2020-01-10 00:00:00
abstract:BACKGROUND:Mammaglobin (MAM) has been used as a specific molecular marker for breast cancer diagnosis. Recently, several groups of researchers proposed a number of therapeutic strategies targeting this molecule. Some of the strategies are based upon an essential but not demonstrated hypothesis - mammaglobin is associat...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-9-8
更新日期:2009-03-23 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-0759-4
更新日期:2019-02-18 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01340-6
更新日期:2020-06-15 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-015-0206-0
更新日期:2015-05-23 00:00:00
abstract::[This corrects the article DOI: 10.1186/s12935-020-01426-1.]. ...
journal_title:Cancer cell international
pub_type: 已发布勘误
doi:10.1186/s12935-020-01482-7
更新日期:2020-08-18 00:00:00
abstract:Background:Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high morbidity and mortality worldwide. MicroRNAs are key regulators of HCC genesis. However, the regulatory role and underlying mechanisms of microRNA in HCC is still limited. Methods:Cyclin B1 (CCNB1) mRNA levels were examined in...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-0729-x
更新日期:2019-01-14 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-017-0406-x
更新日期:2017-03-02 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-016-0303-8
更新日期:2016-04-02 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-016-0352-z
更新日期:2016-09-29 00:00:00
abstract:BACKGROUND:Cancer cells, even in the presence of available oxygen, have a glycolysis enhancement. The "aerobic glycolysis" is known as the Warburg effect and it is considered one of the fundamental hallmarks of metabolic alteration during malignant transformation. A feature of many tumors is also a change into ions equ...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-014-0077-9
更新日期:2014-08-12 00:00:00
abstract:Background:Thyroid cancer (TC) is the most frequent endocrine malignancy. Long noncoding RNAs (lncRNAs) have been confirmed to act as significant roles in tumor development. The role of lncRNA TMPO-AS1 in TC is still unclear, so it remains to be explored. The aim of the research is to investigate the role and regulator...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01334-4
更新日期:2020-07-08 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-1099-0
更新日期:2020-01-23 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-8-10
更新日期:2008-07-03 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章,评审
doi:10.1186/s12935-020-01518-y
更新日期:2020-09-29 00:00:00
abstract:UNLABELLED: BACKGROUND:Anticancer research resulted in the discovery of a promising antimitotic metabolite, 2-methoxyestradiol. 2-Methoxyestradiol-bis-sulphamate, a bis-sulphamoylated analogue exerts antiproliferative- and antimitotic activity. Investigating the anticancer potential of 2-methoxyestradiol-bis-sulphamat...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-12-37
更新日期:2012-08-20 00:00:00
abstract:: Autoimmune phenomena were identified in many different cases of hematological diseases and solid tumors, which may be due to alterations in the expression and function of the NF-κB signaling pathway. Recently, a number of studies have shown that the deletion or mutation of A20, a negative regulator of NF-κB, is frequ...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-12-44
更新日期:2012-11-07 00:00:00
abstract:Background:Breast cancer is the leading cause of oncological mortality among women. Efficient detection of cancer cells in an early stage and potent therapeutic agents targeting metastatic tumors are highly needed to improve survival rates. Emerging evidence indicates that lncRNAs (long noncoding RNAs) are critical reg...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-018-0638-4
更新日期:2018-09-18 00:00:00
abstract:Background:Long non-coding RNAs (lncRNAs) play significant roles in tumorigenesis and can contribute to identification of novel therapeutic targets for cancers. This paper was aimed at exploring the role of CTBP1 divergent transcript (CTBP1-AS2) in cervical cancer (CC) progression. Methods:qRT-PCR and western blot ass...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01430-5
更新日期:2020-07-28 00:00:00
abstract:Objective:This study aimed to investigate the relationship among miR-145-5p, ANGPT2 and the NOD_LIKE_RECEPTOR pathway, thereby revealing the molecular mechanism of these three factors underlying the proliferation, migration and invasion of gastric cancer (GC) epithelial cells. Methods:qRT-PCR was carried out to detect...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01483-6
更新日期:2020-08-28 00:00:00
abstract:Background:The hypoxic tumor microenvironment accelerates the invasion and migration of colorectal cancer (CRC) cells. The aim of this study was to develop and validate a hypoxia gene signature for predicting the outcome in stage I/II CRC patients that have limited therapeutic options. Methods:The hypoxic gene signatu...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-0964-1
更新日期:2019-09-23 00:00:00
abstract:Background:Many circRNAs have been reported to play important roles in cancer development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNAs in esophageal carcinoma (EC) remains unclear. In the current study, we investigated the potential role of circPVT...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-0985-9
更新日期:2019-10-15 00:00:00
abstract:Background:Pancreatic cancer is a common malignant tumor of the digestive tract. It has a high degree of malignancy and poor prognosis. Finding effective molecular markers has great significance for pancreatic cancer diagnosis and treatment. This study aimed to investigate DLGAP5 expression in pancreatic cancer and exp...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01474-7
更新日期:2020-08-08 00:00:00