Overexpression of PSAT1 promotes metastasis of lung adenocarcinoma by suppressing the IRF1-IFNγ axis
An increasing number of enzymes involved in serine biosynthesis have been identified and correlated with malignant evolution in various types of cancer. Here we showed that the overexpression of phosphoserine aminotransferase 1 (PSAT1) is widely found in lung cancer tissues compared with nontumor ti...
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| Veröffentlicht in: | Oncogene 2020-03, Vol.39 (12), p.2509-2522 |
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| creator | Chan, Yung-Chieh Chang, Yu-Chan Chuang, Hsiang-Hao Yang, Yi-Chieh Lin, Yuan-Feng Huang, Ming-Shyan Hsiao, Michael Yang, Chih-Jen Hua, Kuo-Tai |
| description | An increasing number of enzymes involved in serine biosynthesis have been identified and correlated with malignant evolution in various types of cancer. Here we showed that the overexpression of phosphoserine aminotransferase 1 (PSAT1) is widely found in lung cancer tissues compared with nontumor tissues and predicts a poorer prognosis in patients with lung adenocarcinoma. PSAT1 expression was examined in a tissue microarray by immunohistochemistry. The data show that the knockdown of PSAT1 dramatically inhibits the in vitro and in vivo metastatic potential of highly metastatic lung cancer cells; conversely, the enforced expression of exogenous PSAT1 predominantly enhances the metastatic potential of lung cancer cells. Importantly, manipulating PSAT1 expression regulates the in vivo tumor metastatic abilities in lung cancer cells. Adjusting the glucose and glutamine concentrations did not alter the PSAT1-driven cell invasion properties, indicating that this process might not rely on the activation of its enzymatic function. RNA microarray analysis of transcriptional profiling from PSAT1 alternation in CL1-5 and CL1-0 cells demonstrated that interferon regulatory factor 1 (IRF1) acts as a crucial regulator of PSAT1-induced gene expression upon metastatic progression. Decreasing the IRF1-IFIH1 axis compromised the PSAT1-prompted transcriptional reprogramming in cancer cells. Our results identify PSAT1 as a key regulator by a novel PSAT1/IRF1 axis in lung cancer progression, which may serve as a potential biomarker and therapeutic target for the treatment of lung cancer patients. |
| doi_str_mv | 10.1038/s41388-020-1160-4 |
| format | Article |
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Here we showed that the overexpression of phosphoserine aminotransferase 1 (PSAT1) is widely found in lung cancer tissues compared with nontumor tissues and predicts a poorer prognosis in patients with lung adenocarcinoma. PSAT1 expression was examined in a tissue microarray by immunohistochemistry. The data show that the knockdown of PSAT1 dramatically inhibits the in vitro and in vivo metastatic potential of highly metastatic lung cancer cells; conversely, the enforced expression of exogenous PSAT1 predominantly enhances the metastatic potential of lung cancer cells. Importantly, manipulating PSAT1 expression regulates the in vivo tumor metastatic abilities in lung cancer cells. Adjusting the glucose and glutamine concentrations did not alter the PSAT1-driven cell invasion properties, indicating that this process might not rely on the activation of its enzymatic function. RNA microarray analysis of transcriptional profiling from PSAT1 alternation in CL1-5 and CL1-0 cells demonstrated that interferon regulatory factor 1 (IRF1) acts as a crucial regulator of PSAT1-induced gene expression upon metastatic progression. Decreasing the IRF1-IFIH1 axis compromised the PSAT1-prompted transcriptional reprogramming in cancer cells. Our results identify PSAT1 as a key regulator by a novel PSAT1/IRF1 axis in lung cancer progression, which may serve as a potential biomarker and therapeutic target for the treatment of lung cancer patients.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/s41388-020-1160-4</identifier><identifier>PMID: 31988456</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/105 ; 38/61 ; 631/67/1612 ; 631/67/322 ; 64/60 ; Adenocarcinoma ; Adenocarcinoma of Lung - enzymology ; Adenocarcinoma of Lung - genetics ; Adenocarcinoma of Lung - metabolism ; Adenocarcinoma of Lung - pathology ; Animals ; Apoptosis ; Cell Biology ; Cohort Studies ; Disease Progression ; DNA microarrays ; Gene expression ; Gene Knockdown Techniques ; Glutamine ; Human Genetics ; Humans ; Immunohistochemistry ; Interferon regulatory factor ; Interferon regulatory factor 1 ; Interferon Regulatory Factor-1 - antagonists & inhibitors ; Interferon Regulatory Factor-1 - metabolism ; Interferon-gamma - antagonists & inhibitors ; Interferon-gamma - metabolism ; Internal Medicine ; Lung cancer ; Lung Neoplasms - enzymology ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Male ; Medicine ; Medicine & Public Health ; Metastases ; Metastasis ; Mice ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Oncology ; Phosphoserine ; Phosphoserine aminotransferase ; RNA, Messenger - metabolism ; RNA, Neoplasm - metabolism ; Serine ; Signal Transduction ; Therapeutic applications ; Therapeutic targets ; Tissue Array Analysis ; Transaminases ; Transcription ; Up-Regulation ; γ-Interferon</subject><ispartof>Oncogene, 2020-03, Vol.39 (12), p.2509-2522</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020</rights><rights>2020© The Author(s), under exclusive licence to Springer Nature Limited 2020</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-3c33a3bc7d09f7ca382fb922456beffbd2fa38db0abddea0d07bb4a799c4c7ed3</citedby><cites>FETCH-LOGICAL-c400t-3c33a3bc7d09f7ca382fb922456beffbd2fa38db0abddea0d07bb4a799c4c7ed3</cites><orcidid>0000-0003-0474-9935 ; 0000-0001-8529-9213</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41388-020-1160-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41388-020-1160-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31988456$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chan, Yung-Chieh</creatorcontrib><creatorcontrib>Chang, Yu-Chan</creatorcontrib><creatorcontrib>Chuang, Hsiang-Hao</creatorcontrib><creatorcontrib>Yang, Yi-Chieh</creatorcontrib><creatorcontrib>Lin, Yuan-Feng</creatorcontrib><creatorcontrib>Huang, Ming-Shyan</creatorcontrib><creatorcontrib>Hsiao, Michael</creatorcontrib><creatorcontrib>Yang, Chih-Jen</creatorcontrib><creatorcontrib>Hua, Kuo-Tai</creatorcontrib><title>Overexpression of PSAT1 promotes metastasis of lung adenocarcinoma by suppressing the IRF1-IFNγ axis</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>An increasing number of enzymes involved in serine biosynthesis have been identified and correlated with malignant evolution in various types of cancer. Here we showed that the overexpression of phosphoserine aminotransferase 1 (PSAT1) is widely found in lung cancer tissues compared with nontumor tissues and predicts a poorer prognosis in patients with lung adenocarcinoma. PSAT1 expression was examined in a tissue microarray by immunohistochemistry. The data show that the knockdown of PSAT1 dramatically inhibits the in vitro and in vivo metastatic potential of highly metastatic lung cancer cells; conversely, the enforced expression of exogenous PSAT1 predominantly enhances the metastatic potential of lung cancer cells. Importantly, manipulating PSAT1 expression regulates the in vivo tumor metastatic abilities in lung cancer cells. Adjusting the glucose and glutamine concentrations did not alter the PSAT1-driven cell invasion properties, indicating that this process might not rely on the activation of its enzymatic function. RNA microarray analysis of transcriptional profiling from PSAT1 alternation in CL1-5 and CL1-0 cells demonstrated that interferon regulatory factor 1 (IRF1) acts as a crucial regulator of PSAT1-induced gene expression upon metastatic progression. Decreasing the IRF1-IFIH1 axis compromised the PSAT1-prompted transcriptional reprogramming in cancer cells. Our results identify PSAT1 as a key regulator by a novel PSAT1/IRF1 axis in lung cancer progression, which may serve as a potential biomarker and therapeutic target for the treatment of lung cancer patients.</description><subject>13/105</subject><subject>38/61</subject><subject>631/67/1612</subject><subject>631/67/322</subject><subject>64/60</subject><subject>Adenocarcinoma</subject><subject>Adenocarcinoma of Lung - enzymology</subject><subject>Adenocarcinoma of Lung - genetics</subject><subject>Adenocarcinoma of Lung - metabolism</subject><subject>Adenocarcinoma of Lung - pathology</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Cell Biology</subject><subject>Cohort Studies</subject><subject>Disease Progression</subject><subject>DNA microarrays</subject><subject>Gene expression</subject><subject>Gene Knockdown Techniques</subject><subject>Glutamine</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Interferon regulatory factor</subject><subject>Interferon regulatory factor 1</subject><subject>Interferon Regulatory Factor-1 - antagonists & inhibitors</subject><subject>Interferon Regulatory Factor-1 - metabolism</subject><subject>Interferon-gamma - antagonists & inhibitors</subject><subject>Interferon-gamma - metabolism</subject><subject>Internal Medicine</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - enzymology</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Metastasis</subject><subject>Oncology</subject><subject>Phosphoserine</subject><subject>Phosphoserine aminotransferase</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA, Neoplasm - metabolism</subject><subject>Serine</subject><subject>Signal Transduction</subject><subject>Therapeutic applications</subject><subject>Therapeutic targets</subject><subject>Tissue Array Analysis</subject><subject>Transaminases</subject><subject>Transcription</subject><subject>Up-Regulation</subject><subject>γ-Interferon</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kMlKBDEQhoMoOi4P4EUCnqOVpSedo4ijA6Licg7ZWlvs7jHpFn0u38NnMkO7nBQKCur_66_iQ2iXwgEFXh4mQXlZEmBAKJ0CEStoQoWckqJQYhVNQBVAFONsA22m9AgAUgFbRxucqrIUxXSCwuVLiOF1EUNKddfirsJXN0e3FC9i13R9SLgJvUm56rQUn4b2Hhsf2s6Z6Oq2awy2bzgNizEiq_1DwPPrGSXz2cXHOzavddpGa5V5SmHnq2-hu9nJ7fEZOb88nR8fnRMnAHrCHeeGWyc9qEo6w0tWWcVY_tSGqrKeVXnmLRjrfTDgQVorjFTKCSeD51tof8zN3z8PIfX6sRtim09qlrlIXhYl_9fFpSq4UoXILjq6XOxSiqHSi1g3Jr5pCnqJX4_4dcavl_j1cmfvK3mwTfA_G9-8s4GNhpSl9j7E39N_p34CKHuRaw</recordid><startdate>20200301</startdate><enddate>20200301</enddate><creator>Chan, Yung-Chieh</creator><creator>Chang, Yu-Chan</creator><creator>Chuang, Hsiang-Hao</creator><creator>Yang, Yi-Chieh</creator><creator>Lin, Yuan-Feng</creator><creator>Huang, Ming-Shyan</creator><creator>Hsiao, Michael</creator><creator>Yang, Chih-Jen</creator><creator>Hua, Kuo-Tai</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><orcidid>https://orcid.org/0000-0003-0474-9935</orcidid><orcidid>https://orcid.org/0000-0001-8529-9213</orcidid></search><sort><creationdate>20200301</creationdate><title>Overexpression of PSAT1 promotes metastasis of lung adenocarcinoma by suppressing the IRF1-IFNγ axis</title><author>Chan, Yung-Chieh ; Chang, Yu-Chan ; Chuang, Hsiang-Hao ; Yang, Yi-Chieh ; Lin, Yuan-Feng ; Huang, Ming-Shyan ; Hsiao, Michael ; Yang, Chih-Jen ; Hua, Kuo-Tai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-3c33a3bc7d09f7ca382fb922456beffbd2fa38db0abddea0d07bb4a799c4c7ed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>13/105</topic><topic>38/61</topic><topic>631/67/1612</topic><topic>631/67/322</topic><topic>64/60</topic><topic>Adenocarcinoma</topic><topic>Adenocarcinoma of Lung - enzymology</topic><topic>Adenocarcinoma of Lung - genetics</topic><topic>Adenocarcinoma of Lung - metabolism</topic><topic>Adenocarcinoma of Lung - pathology</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Cell Biology</topic><topic>Cohort Studies</topic><topic>Disease Progression</topic><topic>DNA microarrays</topic><topic>Gene expression</topic><topic>Gene Knockdown Techniques</topic><topic>Glutamine</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Interferon regulatory factor</topic><topic>Interferon regulatory factor 1</topic><topic>Interferon Regulatory Factor-1 - antagonists & inhibitors</topic><topic>Interferon Regulatory Factor-1 - metabolism</topic><topic>Interferon-gamma - antagonists & inhibitors</topic><topic>Interferon-gamma - metabolism</topic><topic>Internal Medicine</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - enzymology</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - 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Here we showed that the overexpression of phosphoserine aminotransferase 1 (PSAT1) is widely found in lung cancer tissues compared with nontumor tissues and predicts a poorer prognosis in patients with lung adenocarcinoma. PSAT1 expression was examined in a tissue microarray by immunohistochemistry. The data show that the knockdown of PSAT1 dramatically inhibits the in vitro and in vivo metastatic potential of highly metastatic lung cancer cells; conversely, the enforced expression of exogenous PSAT1 predominantly enhances the metastatic potential of lung cancer cells. Importantly, manipulating PSAT1 expression regulates the in vivo tumor metastatic abilities in lung cancer cells. Adjusting the glucose and glutamine concentrations did not alter the PSAT1-driven cell invasion properties, indicating that this process might not rely on the activation of its enzymatic function. RNA microarray analysis of transcriptional profiling from PSAT1 alternation in CL1-5 and CL1-0 cells demonstrated that interferon regulatory factor 1 (IRF1) acts as a crucial regulator of PSAT1-induced gene expression upon metastatic progression. Decreasing the IRF1-IFIH1 axis compromised the PSAT1-prompted transcriptional reprogramming in cancer cells. Our results identify PSAT1 as a key regulator by a novel PSAT1/IRF1 axis in lung cancer progression, which may serve as a potential biomarker and therapeutic target for the treatment of lung cancer patients.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31988456</pmid><doi>10.1038/s41388-020-1160-4</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-0474-9935</orcidid><orcidid>https://orcid.org/0000-0001-8529-9213</orcidid></addata></record> |
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| ispartof | Oncogene, 2020-03, Vol.39 (12), p.2509-2522 |
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| subjects | 13/105 38/61 631/67/1612 631/67/322 64/60 Adenocarcinoma Adenocarcinoma of Lung - enzymology Adenocarcinoma of Lung - genetics Adenocarcinoma of Lung - metabolism Adenocarcinoma of Lung - pathology Animals Apoptosis Cell Biology Cohort Studies Disease Progression DNA microarrays Gene expression Gene Knockdown Techniques Glutamine Human Genetics Humans Immunohistochemistry Interferon regulatory factor Interferon regulatory factor 1 Interferon Regulatory Factor-1 - antagonists & inhibitors Interferon Regulatory Factor-1 - metabolism Interferon-gamma - antagonists & inhibitors Interferon-gamma - metabolism Internal Medicine Lung cancer Lung Neoplasms - enzymology Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology Male Medicine Medicine & Public Health Metastases Metastasis Mice Neoplasm Invasiveness Neoplasm Metastasis Oncology Phosphoserine Phosphoserine aminotransferase RNA, Messenger - metabolism RNA, Neoplasm - metabolism Serine Signal Transduction Therapeutic applications Therapeutic targets Tissue Array Analysis Transaminases Transcription Up-Regulation γ-Interferon |
| title | Overexpression of PSAT1 promotes metastasis of lung adenocarcinoma by suppressing the IRF1-IFNγ axis |
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