Hepatocyte Nuclear Factor -1α stimulates cervical cancer cells to migrate and invade through regulating pyruvate kinase L/R.
El factor nuclear del hepatocito-1α estimula las células de cáncer cervical para migrar e invadir a través de la regulación de la piruvato cinasa L/R.
Keywords:
cervical cancer, hepatocyte nuclear factor -1α (HNF-1α), pyruvate kinase L/R(PKLR)
Abstract
This study was aimed to analyze the role of hepatocyte nuclear factor -1α (HNF-1α) in regulating migrative and invasive potentials in cervical cancer via the involvement of pyruvate kinase L/R (PKLR). The expression of HNF-1α and PKLR in cervical cancer tissues classified by tumor size and FIGO (Federation International of Gynecology and Obstetrics) stage were detected by qRT-PCR. The expression correlation between HNF-1α and PKLR in cervical cancer tissues was analyzed by Pearson correlation test. After intervening HNF-1α and PKLR levels in SiHa and Hela cells, their migratory and invasive abilities were examined by the Transwell assay. HNF-1α was upregulated in cervical cancer tissues, particularly those with large tumor size or advanced FIGO stage. PKLR was highly expressed in cervical cancer tissues as well, presenting a positive correlation with the HNF-1α level. Knockdown of HNF-1α attenuated migratory and invasive abilities in SiHa cells, whereas overexpression of HNF-1α enhanced migratory and invasive abilities in SiHa cells. PKLR was able to abolish the regulatory effects of HNF-1α on cervical cancer metastasis. HNF-1α and PKLR synergistically promote cervical cancer to migrate and invade.
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References
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He R, Zhu B, Liu J, Zhang N, Zhang W-H, Mao Y. Women’s cancers in china: a spatio-temporal epidemiology analysis. BMC Women’s Health 2021; 21(1): 116.
Schrem H, Klempnauer J, Borlak J. Liver-enriched transcription factors in liver function and development. Part I: the hepatocyte nuclear factor network and liver specific gene expression. Pharmacol Rev 2002; 54(1):129-158.
Lazarevich NL, Cheremnova OA, Varga EV, Ovchinnikov DA, Kudrjavtseva EI, Morozova OV, Fleishman DI, Engelhardt NV, Duncan SA. Progression of HCC in mice is associated with a downregulation in the expression of hepatocyte nuclear factors. Hepatology 2004; 39(4):1038-1047.
Yamagata K, Oda N, Kaisaki PJ, Menzel S, Furuta H, Vaxillaire M, Southam L, Cox RD, Lathrop GM, Boriraj VV, Chen X, Cox NJ, Oda Y, Yano H, Le Beau MM, Yamada S, Nishigori H, Takeda J, Fajans SS, Hattersley AT, Iwasaki N, Hansen T, Pedersen O, Polonsky KS, Bell GI. Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3). Nature 1996; 384(6608):455-458.
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Morita K, Saruwatari J, Tanaka T, Oniki K, Kajiwara A, Otake K, Ogata Y, Nakagawa K. Associations between the common HNF-1α stimulates migration and invasion in cervical cancer 245 HNF1A gene variant p.I27L (rs1169288) and risk of type 2 diabetes mellitus are influenced by weight. Diabetes Metab 2015; 41(1):91-94.
Liu PP, Ding HQ, Huang SZ, Yang SY, Liu T. Severe congenital hemolytic anemia caused by a novel compound hetero-zygous PKLR gene mutation in a Chinese boy. Chin Med J (Engl) 2019; 132(1):92- 95.
Mathupala SP, Ko YH, Pedersen PL. Hexo-kinase-2 bound to mitochondria: cancer’s stygian link to the “Warburg Effect” and a pivotal target for effective therapy. Semin Cancer Biol 2009; 19(1):17-24.
Nie H, Li J, Yang XM, Cao QZ, Feng MX, Xue F, Wei L, Qin W, Gu J, Xia Q, Zhang ZG. Mineralocorticoid receptor suppresses cancer progression and the Warburg effect by modulating the miR-338-3p-PKLR axis in hepatocellular carcinoma. Hepatology 2015; 62(4):1145-1159.
Fan Z, Fan K, Deng S, Gong Y, Qian Y, Huang Q, Yang C, Cheng H, Jin K, Luo G, Liu C, Yu X. HNF-1a promotes pancreatic cancer growth and apoptosis resistance via its target gene PKLR. Acta Biochim Biophys Sin (Shanghai) 2020; 52(3):241-250.
Torre LA, Islami F, Siegel RL, Ward EM, Jemal A. Global cancer in women: burden and trends. Cancer Epidemiol Biomarkers Prev 2017; 26(4):444-457.
Kessler TA. Cervical cancer: prevention and early detection. Semin Oncol Nurs 2017; 33(2):172-183.
Puisieux A, Pommier RM, Morel AP, Lavial F. Cellular pliancy and the multistep process of tumorigenesis. Cancer Cell 2018; 33(2):164-172.
Sizemore GM, Pitarresi JR, Balakrishnan S, Ostrowski MC. The ETS family of oncogenic transcription factors in solid tumours. Nat Rev Cancer 2017; 17(6):337-351.
Fukui K, Yang Q, Cao Y, Takahashi N, Hatakeyama H, Wang H, Wada J, Zhang Y, Marselli L, Nammo T, Yoneda K, Onishi M, Higashiyama S, Matsuzawa Y, Gonzalez FJ, Weir GC, Kasai H, Shimomura I, Miyagawa J, Wollheim CB, Yamagata K. The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation. Cell Metab 2005; 2(6):373-384.
Weber BN, Chi AW, Chavez A, Yashiro-Ohtani Y, Yang Q, Shestova O, Bhandoola A critical role for TCF-1 in T-lineage specification and differentiation. Nature 2011; 476(7358):63-68.
Noll EM, Eisen C, Stenzinger A, Espinet E, Muckenhuber A, Klein C, Vogel V, Klaus B, Nadler W, Rosli C, Lutz C, Kulke M, Engelhardt J, Zickgraf FM, Espinosa O, Schlesner M, Jiang X, Kopp- Schneider A, Neuhaus P, Bahra M, Sinn BV, Eils R, Giese NA, Hackert T, Strobel O, Werner J, Buchler MW, Weichert W, Trumpp A, Sprick MR. CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma. Nat Med 2016; 22(3):278-287.
Laurent-Puig P, Plomteux O, Bluteau O, Zinzindohoue F, Jeannot E, Dahan K, Kartheuser A, Chapusot C, Cugnenc PH, Zucman-Rossi J. Frequent mutations of hepa-tocyte nuclear factor 1 in colorectal cancer with microsatellite instability. Gastroenterology 2003; 124(5):1311-1314.
Pecina-Slaus N, Kafka A, Tomas D, Markovic L, Okstajner PK, Sukser V, Kruslin B. Wnt signaling transcription factors TCF-1 and LEF-1 are upregulated in malignant astrocytic brain tumors. Histol Histopathol 2014; 29(12):1557-1564.
Ng OH, Erbilgin Y, Firtina S, Celkan T, Karakas Z, Aydogan G, Turkkan E, Yildirmak Y, Timur C, Zengin E, van Dongen JJ, Staal FJ, Ozbek U, Sayitoglu M. Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia. Blood Cancer J 2014; 4:e192.
Hellerbrand C, Amann T, Schlegel J, Wild P, Bataille F, Spruss T, Hartmann A, Bosserhoff AK. The novel gene MIA2 acts as a tumour suppressor in hepatocellular carcinoma. Gut 2008; 57(2):243-251.
Kawaguchi T, Takenoshita M, Kabashima T, Uyeda K. Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein. Proc Natl Acad Sci USA 2001; 98(24):13710-13715.
Yang Y, Zhu G, Dong B, Piao J, Chen L, Lin Z. The NQO1/PKLR axis promotes lymph node metastasis and breast cancer progression by modulating glycolytic reprogramming. Cancer Lett 2019; 453:170-183.
Nguyen A, Loo JM, Mital R, Weinberg EM, Man FY, Zeng Z, Paty PB, Saltz L, Janjigian YY, de Stanchina E, Tavazoie SF. PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis. J Clin Invest 2016; 126(2):681-694.
Published
2021-09-07
How to Cite
Tao, X.-L., Yu, W.-C., Chen, D.-J., Wang, L.-M., Liu, L., & Xing, Q. (2021). Hepatocyte Nuclear Factor -1α stimulates cervical cancer cells to migrate and invade through regulating pyruvate kinase L/R.: El factor nuclear del hepatocito-1α estimula las células de cáncer cervical para migrar e invadir a través de la regulación de la piruvato cinasa L/R. Investigación Clínica, 62(3), 236-246. https://doi.org/10.22209/IC.v62n3a05
Section
Original Works
