PSAT1 Promotes Metastasis via p-AKT/SP1/ITGA2 Axis in Estrogen Receptor-Negative Breast Cancer Cell
<p>PSAT1 overexpressed in ER negative breast cancer with lymph node metastasis. (<b>A</b>) Expression profile of PSAT1 in primary breast cancer tissues (<span class="html-italic">n</span> = 1113) compared with normal breast tissues (<span class="html-italic">n</span> = 113) (TCGA). (<b>B</b>) Expression profile of PSAT1 in ER− breast cancer tissues (<span class="html-italic">n</span> = 238) compared with ER+ tissues (<span class="html-italic">n</span> = 808) (TCGA). (<b>C</b>) Representative images of PSAT1 immunohistochemical staining in breast cancer samples; scale bar, 100 µm. (<b>D</b>) Quantification of positive or negative PSAT1 expression in ER− or ER+ BC samples by Chi-square test. Quantification of positive or negative PSAT1 expression in ER− (<b>E</b>) and ER+ (<b>F</b>) BC samples with corresponding LN status by Chi-square test. TCGA = The Cancer Genome Atlas; ER− = ER negative; ER+ = ER positive; lymph node = LN; BC = breast cancer. * <span class="html-italic">p</span> < 0.05, *** <span class="html-italic">p</span> < 0.001, **** <span class="html-italic">p</span> < 0.0001, ns: no significance.</p> "> Figure 2
<p>PSAT1 knockdown prevented metastasis of ER-negative breast cancer cells. Western blot (<b>A</b>) and qRT-PCR assay (<b>B</b>) showed PSAT1 knockdown and overexpression in BT-549 and HCC1937 cells infected with PSAT1 lentivirus (PSAT1-KD1, PSAT1-KD2 and PSAT1-OE) or control (PSAT1-NC and PSAT1-CON). The values of the PSAT1-NC and PSAT1-CON groups were normalized to 1. (<b>C</b>,<b>F</b>) Image and quantification of adhesion assay, transwell migration, and invasion assays in BT-549 and HCC-1937 cells. The cell numbers of PSAT1-NC and PSAT1-CON group were normalized to 1; scale bar for adhesion assay 200 µm and for transwell migration and invasion assay 100 µm. The wound healing assay revealed PSAT1 knockdown inhibited cell metastasis in BT-549 (<b>D</b>) and HCC1937 (<b>E</b>) cellsThe wound healing assay revealed PSAT1 overexpression promoted cell metastasis in BT-549 (<b>G</b>) and HCC1937 (<b>H</b>) cells; scale bar, 200 µm. Statistical analysis was performed using unpaired two-tailed Student <span class="html-italic">t</span>-test. For (<b>C</b>–<b>H</b>), the results are expressed as the mean ± SD; <span class="html-italic">n</span> = 3. ** <span class="html-italic">p</span> < 0.01, *** <span class="html-italic">p</span> < 0.001, **** <span class="html-italic">p</span> < 0.0001.</p> "> Figure 3
<p>PSAT1 promoted metastasis of ER-negative breast cancer cells in mouse model. Western blot (<b>A</b>) and qRT-PCR (<b>B</b>) were used to analyze PSAT1 expression in PSAT1-knockdown (PSAT1-KD1, PSAT1-KD2) or control (PSAT1-NC) 4T1 cells and PSAT1-overexpression (PSAT1-OE) or vector (PSAT1-CON) 4T1 cells. The adhesion assays, transwell migration assays, or invasion assays (<b>B</b>) showed the cellular transfer ability of the indicated cells. The number of PSAT1-NC or PSAT1-CON cells were normalized to 1. Scale bar for adhesion assays were 200 µm and for transwell migration assays or invasion assays were 100 µm. Images and quantification of BALB/C mice tail vein injection lung metastasis mode with PSAT1 knockdown (<b>C</b>) and PSAT1 overexpression (<b>D</b>) 4T1 cells. The quantification was analyzed using Student’s <span class="html-italic">t</span>-test for comparisons. For (<b>B</b>), the results are expressed as the mean ± SD; <span class="html-italic">n</span> = 3. Lung tissues were resected from mice at 27 days. Lung metastases were counted. (<span class="html-italic">n</span> = 5). ** <span class="html-italic">p</span> < 0.01, *** <span class="html-italic">p</span> < 0.001, **** <span class="html-italic">p</span> < 0.0001.</p> "> Figure 4
<p>PSAT1 promoted metastasis of ER-negative breast cancer cells through upregulation of ITGA2 (<b>A</b>). The volcano maps of all samples. Red dots mean the signal value of up-regulated genes (<span class="html-italic">n</span> = 1276), and blue ones indicate the signal value of down-regulated genes (<span class="html-italic">n</span> = 535) (<b>B</b>). Bubble map of KEGG enrichment analysis for DEGs (<b>C</b>). qRT-PCR is used to validation in the indicated BT-549 cells. The PSAT1 ITGA2 expression was analyzed with western blot (<b>D</b>) and qRT-PCR (<b>E</b>) in the indicated cells. The values of the PSAT1-NC and PSAT1-CON groups were normalized to 1 (<b>F</b>). Immunofluorescence staining showed PSAT1 knockdown reduced ITGA2 expression, but PSAT1 overexpression promoted ITGA2 expression. Scale bar, 50 µm (<b>G</b>). Immunoblot assay of PSAT1 and ITGA2 protein levels in PSAT1-CON, PSAT1-OE, PSAT1-OE+siNC, and PSAT1-OE+siITGA2. The adhesion assay (<b>H</b>) and transwell migration assay (<b>I</b>) of BT-549 cells with PSAT1-CON, PSAT1-OE, PSAT1-OE+siNC, and PSAT1-OE+siITGA2. The cell numbers of PSAT1-CON groups were normalized to 1. Scale bar, 100 µm (<b>J</b>). Wound healing assay showed that silencing ITGA2 abrogates cell metastasis due to PSAT1 overexpression. Scale bar, 200, µm. Statistical analysis was performed with unpaired two-tailed Student <span class="html-italic">t</span>-test. For (<b>H</b>–<b>J</b>), the results are expressed as the mean ± SD; <span class="html-italic">n</span> = 3. #ITGA2 level compared to PSAT1-NC or PSAT1-CON. * <span class="html-italic">p</span> < 0.05, ** <span class="html-italic">p</span> < 0.01, *** <span class="html-italic">p</span> < 0.001, **** <span class="html-italic">p</span> < 0.0001, ### <span class="html-italic">p</span> < 0.001, #### <span class="html-italic">p</span> < 0.0001, ns: no significance. DEGs: differentially expressed genes.</p> "> Figure 5
<p>PSAT1 upregulated ITGA2 expression through transcription factors SP1 (<b>A</b>). Western blot was performed to analyze the expression of SP1 in nucleus and cytoplasm of indicated cells (<b>B</b>). Schematic representation of the predicated SP1 binding site within the ITGA2 promotor (<b>C</b>). Binding of SP1 to the ITGA2 promoter region in vitro was assessed using ChIP with anti-SP1 or anti-IgG antibodies in BT-549 cells. Input DNA purified by ChIP assay were measured using qRT-PCR. The results of IgG were normalized to 1 (<b>D</b>). Western blot was used to show PSAT1 and ITGA2 protein levels in PSAT1-CON, PSAT1-OE, PSAT1-OE+DMSO, and PSAT1-OE+MIT (<b>E</b>). qRT-PCR quantification of the indicated mRNAs in BT-549 cells (<b>F</b>). Wound healing assay showed that silencing SP1 abrogates cell metastasis caused by PSAT1 overexpression. Scale bar, 200 µm. The adhesion assay (<b>G</b>) and transwell migration assay (h) of BT-549 cells with PSAT1-CON, PSAT1-OE, PSAT1-OE+DMSO, and PSAT1-OE+MIT. Scale bar, 100 µm. Statistical analysis was performed with unpaired two-tailed Student <span class="html-italic">t</span>-test. For (<b>D</b>–<b>H</b>), treated with MIT (40 μM) for 24 h. For (<b>F</b>–<b>H</b>), the results are expressed as the mean ± SD; <span class="html-italic">n</span> = 3. For <span class="html-italic">p</span> values in e *PSAT1 level compared to PSAT1-CON; #ITGA2 level compared to PSAT1-CON; ^ITGA2 level compared to PSAT1-OE+DMSO. * <span class="html-italic">p</span> < 0.05, ** <span class="html-italic">p</span> < 0.01, *** <span class="html-italic">p</span> < 0.001, **** <span class="html-italic">p</span> < 0.0001, ### <span class="html-italic">p</span> < 0.001, #### <span class="html-italic">p</span> < 0.0001, ^^^ <span class="html-italic">p</span> < 0.001, ns: no significance.</p> "> Figure 6
<p>PSAT1 promoted metastasis of ER-negative breast cancer cells by p-AKT/SP1/ITGA2 axis (<b>A</b>). Western blot was performed to analyze the expression of PSAT1 and AKT/p-AKT in the indicated cells (<b>B</b>). PSAT1 overexpression cell treated with PI3K-AKT pathway inhibitor. Then the expression of P-AKT and ITGA2 were tested (<b>C</b>). Western blot was used to show PSAT1, SP1, and ITGA2 protein levels in PSAT1-CON, PSAT1-OE, PSAT1-OE+DMSO, and PSAT1-OE+LY294002 (<b>D</b>). qRT-PCR quantification of the indicated mRNAs in BT-549 cells (<b>E</b>). The adhesion assay and transwell migration assay of BT-549 cells showed that silencing p-AKT pathway abrogates cell metastasis caused by PSAT1 overexpression. Statistical analysis was performed using unpaired two-tailed Student <span class="html-italic">t</span>-test (<b>F</b>). Proposed model for PSAT1 promotes estrogen receptor negative breast cancer cell metastasis via p-AKT/SP1/ITGA2 pathway. For (<b>C</b>–<b>E</b>), treated with LY294002 (10 μM) for 1 h. For (<b>E</b>), the results are expressed as the mean ± SD; <span class="html-italic">n</span> = 3. For <span class="html-italic">p</span> values in e *PSAT1 level compared to PSAT1-CON; #ITGA2 level compared to PSAT1-CON; ^ITGA2 level compared to PSAT1-OE+DMSO. ** <span class="html-italic">p</span> < 0.01, *** <span class="html-italic">p</span> < 0.001, **** <span class="html-italic">p</span> < 0.0001, #### <span class="html-italic">p</span> < 0.0001, ^^^^ <span class="html-italic">p</span> < 0.0001, ns: no significance.</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents
2.2. Cell Lines and Culture
2.3. Cell Transfection and Lentiviruses Infection
2.4. Phenotypic Experiment
2.5. Patients and Tissue Specimens
2.6. Immunohistochemistry
2.7. Immunofluorescence Staining
2.8. Western Blotting and Antibodies
2.9. Animal Experiments
2.10. RNA Isolation and qRT-PCR
2.11. Chromatin Immunoprecipitation
2.12. RNA-Sequencing Analysis
2.13. Public Data Access
2.14. Statistics
3. Results
3.1. PSAT1 Is Overexpressed in ER-Negative Breast Cancer with Lymph Node Metastasis
3.2. PSAT1 Facilitates the Metastasis of ER-Negative Breast Cancer Cells
3.3. PSAT1 Promotes the Metastasis of ER-Negative Breast Cancer Cells In Vivo
3.4. PSAT1 Enhances ER-Negative Breast Cancer Metastasis through the Upregulation of ITGA2
3.5. PSAT1 Regulated ITGA2 Expression through SP1
3.6. PSAT1-Regulated Tumor Metastasis via the p-AKT/SP1/ITGA2 Axis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer statistics, 2022. CA A Cancer J. Clin. 2022, 72, 7–33. [Google Scholar] [CrossRef] [PubMed]
- Russnes, H.G.; Lingjærde, O.C.; Børresen-Dale, A.L.; Caldas, C. Breast Cancer Molecular Stratification: From Intrinsic Subtypes to Integrative Clusters. Am. J. Pathol. 2017, 187, 2152–2162. [Google Scholar] [CrossRef] [PubMed]
- Johansson, A.L.V.; Trewin, C.B.; Fredriksson, I.; Reinertsen, K.V.; Russnes, H.; Ursin, G. In modern times, how important are breast cancer stage, grade and receptor subtype for survival: A population-based cohort study. Breast Cancer Res. 2021, 23, 17. [Google Scholar] [CrossRef] [PubMed]
- Goldhirsch, A.; Wood, W.C.; Coates, A.S.; Gelber, R.D.; Thürlimann, B.; Senn, H.J. Strategies for subtypes—Dealing with the diversity of breast cancer: Highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2011, 22, 1736–1747. [Google Scholar] [CrossRef] [PubMed]
- Kunc, M.; Biernat, W.; Senkus-Konefka, E. Estrogen receptor-negative progesterone receptor-positive breast cancer—“Nobody’s land” or just an artifact? Cancer Treat. Rev. 2018, 67, 78–87. [Google Scholar] [CrossRef] [PubMed]
- Santa-Maria, C.A.; Gradishar, W.J. Changing Treatment Paradigms in Metastatic Breast Cancer: Lessons Learned. JAMA Oncol. 2015, 1, 528–534. [Google Scholar] [CrossRef] [PubMed]
- Waks, A.G.; Winer, E.P. Breast Cancer Treatment: A Review. JAMA 2019, 321, 288–300. [Google Scholar] [CrossRef]
- Possemato, R.; Marks, K.M.; Shaul, Y.D.; Pacold, M.E.; Kim, D.; Birsoy, K.; Sethumadhavan, S.; Woo, H.K.; Jang, H.G.; Jha, A.K.; et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 2011, 476, 346–350. [Google Scholar] [CrossRef] [PubMed]
- Li, A.M.; Ducker, G.S.; Li, Y.; Seoane, J.A.; Xiao, Y.; Melemenidis, S.; Zhou, Y.; Liu, L.; Vanharanta, S.; Graves, E.E.; et al. Metabolic Profiling Reveals a Dependency of Human Metastatic Breast Cancer on Mitochondrial Serine and One-Carbon Unit Metabolism. Mol. Cancer Res. 2020, 18, 599–611. [Google Scholar] [CrossRef]
- Baek, J.Y.; Jun, D.Y.; Taub, D.; Kim, Y.H. Characterization of human phosphoserine aminotransferase involved in the phosphorylated pathway of L-serine biosynthesis. Biochem. J. 2003, 373, 191–200. [Google Scholar] [CrossRef]
- Ma, L.; Tao, Y.; Duran, A.; Llado, V.; Galvez, A.; Barger, J.F.; Castilla, E.A.; Chen, J.; Yajima, T.; Porollo, A.; et al. Control of nutrient stress-induced metabolic reprogramming by PKCζ in tumorigenesis. Cell 2013, 152, 599–611. [Google Scholar] [CrossRef] [PubMed]
- Yang, M.; Vousden, K.H. Serine and one-carbon metabolism in cancer. Nat. Rev. Cancer 2016, 16, 650–662. [Google Scholar] [CrossRef]
- Jin, H.O.; Hong, S.E.; Kim, J.Y.; Jang, S.K.; Kim, Y.S.; Sim, J.H.; Oh, A.C.; Kim, H.; Hong, Y.J.; Lee, J.K.; et al. Knock-down of PSAT1 Enhances Sensitivity of NSCLC Cells to Glutamine-limiting Conditions. Anticancer Res. 2019, 39, 6723–6730. [Google Scholar] [CrossRef] [PubMed]
- Cai, L.Y.; Chen, S.J.; Xiao, S.H.; Sun, Q.J.; Ding, C.H.; Zheng, B.N.; Zhu, X.Y.; Liu, S.Q.; Yang, F.; Yang, Y.X.; et al. Targeting p300/CBP Attenuates Hepatocellular Carcinoma Progression through Epigenetic Regulation of Metabolism. Cancer Res. 2021, 81, 860–872. [Google Scholar] [CrossRef] [PubMed]
- Vie, N.; Copois, V.; Bascoul-Mollevi, C.; Denis, V.; Bec, N.; Robert, B.; Fraslon, C.; Conseiller, E.; Molina, F.; Larroque, C.; et al. Overexpression of phosphoserine aminotransferase PSAT1 stimulates cell growth and increases chemoresistance of colon cancer cells. Mol. Cancer 2008, 7, 14. [Google Scholar] [CrossRef] [PubMed]
- Gao, S.; Ge, A.; Xu, S.; You, Z.; Ning, S.; Zhao, Y.; Pang, D. PSAT1 is regulated by ATF4 and enhances cell proliferation via the GSK3beta/beta-catenin/cyclin D1 signaling pathway in ER-negative breast cancer. J. Exp. Clin. Cancer Res. 2017, 36, 179. [Google Scholar] [CrossRef]
- Zhu, S.; Wang, X.; Liu, L.; Ren, G. Stabilization of Notch1 and beta-catenin in response to ER-breast cancer-specific up-regulation of PSAT1 mediates distant metastasis. Transl. Oncol. 2022, 20, 101399. [Google Scholar] [CrossRef]
- Luo, M.Y.; Zhou, Y.; Gu, W.M.; Wang, C.; Shen, N.X.; Dong, J.K.; Lei, H.M.; Tang, Y.B.; Liang, Q.; Zou, J.H.; et al. Metabolic and Nonmetabolic Functions of PSAT1 Coordinate Signaling Cascades to Confer EGFR Inhibitor Resistance and Drive Progression in Lung Adenocarcinoma. Cancer Res. 2022, 82, 3516–3531. [Google Scholar] [CrossRef]
- Lin, J.; Song, T.; Li, C.; Mao, W. GSK-3β in DNA repair, apoptosis, and resistance of chemotherapy, radiotherapy of cancer. Biochimica et biophysica acta. Mol. Cell Res. 2020, 1867, 118659. [Google Scholar]
- Miricescu, D.; Totan, A.; Stanescu, S., II; Badoiu, S.C.; Stefani, C.; Greabu, M. PI3K/AKT/mTOR Signaling Pathway in Breast Cancer: From Molecular Landscape to Clinical Aspects. Int. J. Mol. Sci. 2020, 22, 173. [Google Scholar] [CrossRef]
- Albelda, S.M.; Buck, C.A. Integrins and other cell adhesion molecules. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 1990, 4, 2868–2880. [Google Scholar] [CrossRef]
- Ren, D.; Zhao, J.; Sun, Y.; Li, D.; Meng, Z.; Wang, B.; Fan, P.; Liu, Z.; Jin, X.; Wu, H. Overexpressed ITGA2 promotes malignant tumor aggression by up-regulating PD-L1 expression through the activation of the STAT3 signaling pathway. J. Exp. Clin. Cancer Res. 2019, 38, 485. [Google Scholar] [CrossRef] [PubMed]
- Adorno-Cruz, V.; Hoffmann, A.D.; Liu, X.; Dashzeveg, N.K.; Taftaf, R.; Wray, B.; Keri, R.A.; Liu, H. ITGA2 promotes expression of ACLY and CCND1 in enhancing breast cancer stemness and metastasis. Genes Dis. 2021, 8, 493–508. [Google Scholar] [CrossRef] [PubMed]
- Gaballa, R.; Ali, H.E.A.; Mahmoud, M.O.; Rhim, J.S.; Ali, H.I.; Salem, H.F.; Saleem, M.; Kandeil, M.A.; Ambs, S.; Abd Elmageed, Z.Y. Exosomes-Mediated Transfer of Itga2 Promotes Migration and Invasion of Prostate Cancer Cells by Inducing Epithelial-Mesenchymal Transition. Cancers 2020, 12, 2300. [Google Scholar] [CrossRef] [PubMed]
- Cheli, Y.; Kanaji, S.; Jacquelin, B.; Chang, M.; Nugent, D.J.; Kunicki, T.J. Transcriptional and epigenetic regulation of the integrin collagen receptor locus ITGA1-PELO-ITGA2. Biochim. Biophys. Acta 2007, 1769, 546–558. [Google Scholar] [CrossRef] [PubMed]
- Jacquelin, B.; Rozenshteyn, D.; Kanaji, S.; Koziol, J.A.; Nurden, A.T.; Kunicki, T.J. Characterization of Inherited Differences in Transcription of the Human Integrin alpha 2 Gene. J. Biol. Chem. 2001, 276, 23518–23524. [Google Scholar] [CrossRef]
- Zhu, H.; Wang, S.; Shen, H.; Zheng, X.; Xu, X. SP1/AKT/FOXO3 Signaling Is Involved in miR-362-3p-Mediated Inhibition of Cell-Cycle Pathway and EMT Progression in Renal Cell Carcinoma. Front. Cell Dev. Biol. 2020, 8, 297. [Google Scholar] [CrossRef]
- Zhang, G.; Xia, B.; Liu, T.; Zhang, J.; Niu, M.; Xu, S.; Bai, X.; You, Z.; Xu, Q.; Zhang, Y.; et al. A High-Quality Biobank Supports Breast Cancer Research in Harbin, China. Biopreservation Biobanking 2016, 14, 375–382. [Google Scholar] [CrossRef]
- Goldman, M.J.; Craft, B.; Hastie, M.; Repečka, K.; McDade, F.; Kamath, A.; Banerjee, A.; Luo, Y.; Rogers, D.; Brooks, A.N.; et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat. Biotechnol. 2020, 38, 675–678. [Google Scholar] [CrossRef]
- Liu, Y.; Zhang, P.; Wu, Q.; Fang, H.; Wang, Y.; Xiao, Y.; Cong, M.; Wang, T.; He, Y.; Ma, C.; et al. Long non-coding RNA NR2F1-AS1 induces breast cancer lung metastatic dormancy by regulating NR2F1 and ΔNp63. Nat. Commun. 2021, 12, 5232. [Google Scholar] [CrossRef]
- Sato, M.; Matsumoto, M.; Saiki, Y.; Alam, M.; Nishizawa, H.; Rokugo, M.; Brydun, A.; Yamada, S.; Kaneko, M.K.; Funayama, R.; et al. BACH1 Promotes Pancreatic Cancer Metastasis by Repressing Epithelial Genes and Enhancing Epithelial-Mesenchymal Transition. Cancer Res. 2020, 80, 1279–1292. [Google Scholar] [CrossRef]
- Xu, C.; Ding, Y.H.; Wang, K.; Hao, M.; Li, H.; Ding, L. Claudin-7 deficiency promotes stemness properties in colorectal cancer through Sox9-mediated Wnt/β-catenin signalling. J. Transl. Med. 2021, 19, 311. [Google Scholar] [CrossRef] [PubMed]
- Bartolini, A.; Cardaci, S.; Lamba, S.; Oddo, D.; Marchiò, C.; Cassoni, P.; Amoreo, C.A.; Corti, G.; Testori, A.; Bussolino, F.; et al. BCAM and LAMA5 Mediate the Recognition between Tumor Cells and the Endothelium in the Metastatic Spreading of KRAS-Mutant Colorectal Cancer. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2016, 22, 4923–4933. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Wang, Z.; Huang, R.; Lu, Z.; Chen, X.; Huang, D. UPP1 Promotes Lung Adenocarcinoma Progression through Epigenetic Regulation of Glycolysis. Aging Dis. 2022, 13, 1488–1503. [Google Scholar] [CrossRef] [PubMed]
- Ha, H.; Debnath, B.; Neamati, N. Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases. Theranostics 2017, 7, 1543–1588. [Google Scholar] [CrossRef] [PubMed]
- Chan, Y.C.; Chang, Y.C.; Chuang, H.H.; Yang, Y.C.; Lin, Y.F.; Huang, M.S.; Hsiao, M.; Yang, C.J.; Hua, K.T. Overexpression of PSAT1 promotes metastasis of lung adenocarcinoma by suppressing the IRF1-IFNgamma axis. Oncogene 2020, 39, 2509–2522. [Google Scholar] [CrossRef] [PubMed]
- Montrose, D.C.; Saha, S.; Foronda, M.; McNally, E.M.; Chen, J.; Zhou, X.K.; Ha, T.; Krumsiek, J.; Buyukozkan, M.; Verma, A.; et al. Exogenous and Endogenous Sources of Serine Contribute to Colon Cancer Metabolism, Growth, and Resistance to 5-Fluorouracil. Cancer Res. 2021, 81, 2275–2288. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Li, J.; Dong, X.; Meng, D.; Zhi, X.; Yuan, L.; Yao, L. PSAT1 Regulated Oxidation-Reduction Balance Affects the Growth and Prognosis of Epithelial Ovarian Cancer. Onco Targets Ther. 2020, 13, 5443–5453. [Google Scholar] [CrossRef]
- Li, S.; Yang, H.; Li, W.; Liu, J.Y.; Ren, L.W.; Yang, Y.H.; Ge, B.B.; Zhang, Y.Z.; Fu, W.Q.; Zheng, X.J.; et al. ADH1C inhibits progression of colorectal cancer through the ADH1C/PHGDH/PSAT1/serine metabolic pathway. Acta Pharmacol. Sin. 2022, 43, 2709–2722. [Google Scholar] [CrossRef]
- Li, M.K.; Liu, L.X.; Zhang, W.Y.; Zhan, H.L.; Chen, R.P.; Feng, J.L.; Wu, L.F. Long noncoding RNA MEG3 suppresses epithelialtomesenchymal transition by inhibiting the PSAT1dependent GSK3beta/Snail signaling pathway in esophageal squamous cell carcinoma. Oncol. Rep. 2020, 44, 2130–2142. [Google Scholar]
- Metcalf, S.; Dougherty, S.; Kruer, T.; Hasan, N.; Biyik-Sit, R.; Reynolds, L.; Clem, B.F. Selective loss of phosphoserine aminotransferase 1 (PSAT1) suppresses migration, invasion, and experimental metastasis in triple negative breast cancer. Clin. Exp. Metastasis 2020, 37, 187–197. [Google Scholar] [CrossRef] [PubMed]
- Tandon, M.; Othman, A.H.; Winogradzki, M.; Pratap, J. Bone metastatic breast cancer cells display downregulation of PKC-zeta with enhanced glutamine metabolism. Gene 2021, 775, 145419. [Google Scholar] [CrossRef]
- Metcalf, S.; Petri, B.J.; Kruer, T.; Green, B.; Dougherty, S.; Wittliff, J.L.; Klinge, C.M.; Clem, B.F. Serine synthesis influences tamoxifen response in ER+ human breast carcinoma. Endocr. Relat. Cancer 2021, 28, 27–37. [Google Scholar] [CrossRef]
- Pan, H.; Wanami, L.S.; Dissanayake, T.R.; Bachelder, R.E. Autocrine semaphorin3A stimulates alpha2 beta1 integrin expression/function in breast tumor cells. Breast Cancer Res. Treat. 2009, 118, 197–205. [Google Scholar] [CrossRef] [PubMed]
- Chuang, Y.C.; Wu, H.Y.; Lin, Y.L.; Tzou, S.C.; Chuang, C.H.; Jian, T.Y.; Chen, P.R.; Chang, Y.C.; Lin, C.H.; Huang, T.H.; et al. Blockade of ITGA2 Induces Apoptosis and Inhibits Cell Migration in Gastric Cancer. Biol. Proced. Online 2018, 20, 10. [Google Scholar] [CrossRef]
- Altomare, D.A.; Testa, J.R. Perturbations of the AKT signaling pathway in human cancer. Oncogene 2005, 24, 7455–7464. [Google Scholar] [CrossRef] [PubMed]
- Revathidevi, S.; Munirajan, A.K. Akt in cancer: Mediator and more. Semin. Cancer Biol. 2019, 59, 80–91. [Google Scholar] [CrossRef]
- Manning, B.D.; Toker, A. AKT/PKB Signaling: Navigating the Network. Cell 2017, 169, 381–405. [Google Scholar] [CrossRef] [PubMed]
- Martens, J.W.; Nimmrich, I.; Koenig, T.; Look, M.P.; Harbeck, N.; Model, F.; Kluth, A.; Bolt-de Vries, J.; Sieuwerts, A.M.; Portengen, H.; et al. Association of DNA methylation of phosphoserine aminotransferase with response to endocrine therapy in patients with recurrent breast cancer. Cancer Res. 2005, 65, 4101–4117. [Google Scholar] [CrossRef]
- Choi, B.H.; Rawat, V.; Hogstrom, J.; Burns, P.A.; Conger, K.O.; Ozgurses, M.E.; Patel, J.M.; Mehta, T.S.; Warren, A.; Selfors, L.M.; et al. Lineage-specific silencing of PSAT1 induces serine auxotrophy and sensitivity to dietary serine starvation in luminal breast tumors. Cell Rep. 2022, 38, 110278. [Google Scholar] [CrossRef]
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Zhang, X.; Wang, S.; Li, W.; Wang, J.; Gong, Y.; Chen, Q.; Cao, S.; Pang, D.; Gao, S. PSAT1 Promotes Metastasis via p-AKT/SP1/ITGA2 Axis in Estrogen Receptor-Negative Breast Cancer Cell. Biomolecules 2024, 14, 990. https://doi.org/10.3390/biom14080990
Zhang X, Wang S, Li W, Wang J, Gong Y, Chen Q, Cao S, Pang D, Gao S. PSAT1 Promotes Metastasis via p-AKT/SP1/ITGA2 Axis in Estrogen Receptor-Negative Breast Cancer Cell. Biomolecules. 2024; 14(8):990. https://doi.org/10.3390/biom14080990
Chicago/Turabian StyleZhang, Xingda, Siyu Wang, Wei Li, Jianyu Wang, Yajie Gong, Quanrun Chen, Shihan Cao, Da Pang, and Song Gao. 2024. "PSAT1 Promotes Metastasis via p-AKT/SP1/ITGA2 Axis in Estrogen Receptor-Negative Breast Cancer Cell" Biomolecules 14, no. 8: 990. https://doi.org/10.3390/biom14080990