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.
Hepatocyte Nuclear Factor -1α stimulates cervical cancer cells to migrate and invade through regulating pyruvate kinase L/R.
Palabras clave:
cáncer de cuello uterino, factor nuclear del hepatocito -1α (HNF-1α), piruvato quinasa L/R (PKLR)
Resumen
Este estudio tuvo como objetivo analizar el papel del factor nuclear del hepatocito -1α (HNF-1α) en la regulación de los potenciales migratorios e invasivos en el cáncer de cuello uterino a través de la participación de la piruvato quinasa L/R (PKLR). Se detectó mediante qRT-PCR, la expresión de HNF-1α y PKLR en tejidos de cáncer de cuello uterino, clasificados de acuerdo al tamaño del tumor y su estadio FIGO (Federación Internacional de Ginecología y Obstetricia). La correlación de expresión entre HNF-1α y PKLR en tejidos de cáncer de cuello uterino se analizó mediante la prueba de correlación de Pearson. Después de intervenir los niveles de HNF-1α y PKLR en las células SiHa y Hela, se examinaron las capacidades migratorias e invasivas mediante el ensayo Transwell. HNF-1α se reguló positivamente en tejidos de cáncer de cuello uterino, en particular aquellos con tumores de gran tamaño o estadio FIGO avanzado. PKLR también se expresó en gran medida en los tejidos del cáncer de cuello uterino, presentando una correlación positiva con el nivel de HNF-1α. La eliminación de HNF-1α atenuó las capacidades migratorias e invasivas en las células SiHa, mientras que la sobreexpresión de HNF-1α aumentó las capacidades migratorias e invasivas en las células SiHa. La PKLR pudo abolir los efectos reguladores del HNF-1α sobre la metástasis del cáncer de cuello uterino. HNF-1α y PKLR promueven sinérgicamente la invasión y migración del cáncer de cuello.
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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.
Estrada K, Aukrust I, Bjorkhaug L, Burtt NP, Mercader JM, Garcia-Ortiz H, Huerta- Chagoya A, Moreno-Macias H, Walford G, Flannick J, Williams AL, Gomez-Vazquez MJ, Fernandez-Lopez JC, Martinez-Hernandez A, Jimenez-Morales S, Centeno- Cruz F, Mendoza-Caamal E, Revilla-Monsalve C, Islas-Andrade S, Cordova EJ, Soberon X, Gonzalez-Villalpando ME, Henderson E, Wilkens LR, Le Marchand L, Arellano-Campos O, Ordonez-Sanchez ML, Rodriguez-Torres M, Rodriguez-Guillen R, Riba L, Najmi LA, Jacobs SB, Fennell T, Gabriel S, Fontanillas P, Hanis CL, Lehman DM, Jenkinson CP, Abboud HE, Bell GI, Cortes ML, Boehnke M, Gonzalez- Villalpando C, Orozco L, Haiman CA, Tusie-Luna T, Aguilar-Salinas CA, Altshuler D, Njolstad PR, Florez JC, MacArthur DG. Association of a low-frequency variant in HNF1A with type 2 diabetes in a Latino population. JAMA 2014; 311(22):2305-2314.
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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.
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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.
Publicado
2021-09-07
Cómo citar
Tao, X.-L., Yu, W.-C., Chen, D.-J., Wang, L.-M., Liu, L., & Xing, Q. (2021). 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.: Hepatocyte Nuclear Factor -1α stimulates cervical cancer cells to migrate and invade through regulating pyruvate kinase L/R. Investigación Clínica, 62(3), 236-246. https://doi.org/10.22209/IC.v62n3a05
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