Oncoprotein HBXIP induces PKM2 via transcription factor E2F1 to promote cell proliferation in ER-positive breast cancer
We have reported that hepatitis B X-interacting protein (HBXIP, also termed LAMTOR5) can act as an oncogenic transcriptional co-activator to modulate gene expression, promoting breast cancer development. Pyruvate kinase muscle isozyme M2 (PKM2), encoded by PKM gene, has emerged as a key oncoprotein in breast cancer. Yet, the regulatory mechanism of PKM2 is still unexplored. Here, we report that HBXIP can upregulate PKM2 to accelerate proliferation of estrogen receptor positive (ER+) breast cancer. Immunohistochemistry analysis using breast cancer tissue microarray uncovered a positive association between the expression of HBXIP and PKM2. We also discovered that PKM2 expression was positively related with HBXIP expression in clinical breast cancer patients by real-time PCR assay. Interestingly, in ER+ breast cancer cells, HBXIP was capable of upregulating PKM2 expression at mRNA and protein levels in a dose-dependent manner, as well as increasing the activity of PKM promoter. Mechanistically, HBXIP could stimulate PKM promoter through binding to the -779/-579 promoter region involving co-activation of E2F transcription factor 1 (E2F1). In function, cell viability, EdU, colony formation, and xenograft tumor growth assays showed that HBXIP contributed to accelerating cell proliferation through PKM2 in ER+ breast cancer. Collectively, we conclude that HBXIP induces PKM2 through transcription factor E2F1 to facilitate ER+ breast cancer cell proliferation. We provide new evidence for the mechanism of transcription regulation of PKM2 in promotion of breast cancer progression.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
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| Enthalten in: |
Acta pharmacologica Sinica - 40(2019), 4 vom: 21. Apr., Seite 530-538 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Bo-Wen [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.09.2019 Date Revised 13.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41401-018-0015-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM285697250 |
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| 245 | 1 | 0 | |a Oncoprotein HBXIP induces PKM2 via transcription factor E2F1 to promote cell proliferation in ER-positive breast cancer |
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| 520 | |a We have reported that hepatitis B X-interacting protein (HBXIP, also termed LAMTOR5) can act as an oncogenic transcriptional co-activator to modulate gene expression, promoting breast cancer development. Pyruvate kinase muscle isozyme M2 (PKM2), encoded by PKM gene, has emerged as a key oncoprotein in breast cancer. Yet, the regulatory mechanism of PKM2 is still unexplored. Here, we report that HBXIP can upregulate PKM2 to accelerate proliferation of estrogen receptor positive (ER+) breast cancer. Immunohistochemistry analysis using breast cancer tissue microarray uncovered a positive association between the expression of HBXIP and PKM2. We also discovered that PKM2 expression was positively related with HBXIP expression in clinical breast cancer patients by real-time PCR assay. Interestingly, in ER+ breast cancer cells, HBXIP was capable of upregulating PKM2 expression at mRNA and protein levels in a dose-dependent manner, as well as increasing the activity of PKM promoter. Mechanistically, HBXIP could stimulate PKM promoter through binding to the -779/-579 promoter region involving co-activation of E2F transcription factor 1 (E2F1). In function, cell viability, EdU, colony formation, and xenograft tumor growth assays showed that HBXIP contributed to accelerating cell proliferation through PKM2 in ER+ breast cancer. Collectively, we conclude that HBXIP induces PKM2 through transcription factor E2F1 to facilitate ER+ breast cancer cell proliferation. We provide new evidence for the mechanism of transcription regulation of PKM2 in promotion of breast cancer progression | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a E2F1 | |
| 650 | 4 | |a HBXIP | |
| 650 | 4 | |a PKM2 | |
| 650 | 4 | |a breast cancer | |
| 650 | 4 | |a proliferation | |
| 650 | 7 | |a Adaptor Proteins, Signal Transducing |2 NLM | |
| 650 | 7 | |a Carrier Proteins |2 NLM | |
| 650 | 7 | |a E2F1 Transcription Factor |2 NLM | |
| 650 | 7 | |a LAMTOR5 protein, human |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a Receptors, Estrogen |2 NLM | |
| 650 | 7 | |a Thyroid Hormones |2 NLM | |
| 700 | 1 | |a Wang, Tian-Jiao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Lei-Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yun-Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Jin-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Fei-Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Quan-Sheng |e verfasserin |4 aut | |
| 700 | 1 | |a Bao, Ming-Zhu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wei-Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Li-Hong |e verfasserin |4 aut | |
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