Your browser doesn't support javascript.
loading
Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail.
Veena, Mysore S; Gahng, Jungmo J; Alani, Mustafa; Ko, Albert Y; Basak, Saroj K; Liu, Isabelle Y; Hwang, Kimberly J; Chatoff, Jenna R; Venkatesan, Natarajan; Morselli, Marco; Yan, Weihong; Ali, Ibraheem; Kaczor-Urbanowicz, Karolina Elzbieta; Gowda, Bhavani Shankara; Frost, Patrick; Pellegrini, Matteo; Moatamed, Neda A; Wilczynski, Sharon P; Bomont, Pascale; Wang, Marilene B; Shin, Daniel Sanghoon; Srivatsan, Eri S.
Afiliación
  • Veena MS; Department of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Gahng JJ; Department of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Alani M; Department of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Ko AY; Department of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Basak SK; Department of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Liu IY; Department of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Hwang KJ; Department of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Chatoff JR; Department of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Venkatesan N; Department of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Morselli M; Department of Molecular, Cellular and Developmental Biology, UCLA, Los Angeles, California.
  • Yan W; Department of Chemistry and Biochemistry and the Institute for Quantitative and Computational Biology, UCLA, Los Angeles, California.
  • Ali I; Department of Louise M. Darling Biomedical Library and The Institute for Quantitative and Computational Biology, UCLA, Los Angeles, California.
  • Kaczor-Urbanowicz KE; Department of Oral Biology and Medicine, Center for Oral and Head/Neck Oncology Research, School of Dentistry, UCLA, Los Angeles, California.
  • Gowda BS; The Institute for Quantitative and Computational Biosciences, UCLA, Los Angeles, California.
  • Frost P; Department of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Pellegrini M; Department of Medicine, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Moatamed NA; Department of Molecular, Cellular and Developmental Biology, UCLA, Los Angeles, California.
  • Wilczynski SP; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Bomont P; Department of Pathology, City of Hope National Medical Center, Duarte, California.
  • Wang MB; ERC team, INMG, UCBL Lyon1 - CNRS UMR5261 - INSERM U1315, Université Lyon 1, Université de Lyon, Lyon, France.
  • Shin DS; Department of Surgery, VAGLAHS and Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Srivatsan ES; Department of Medicine, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.
Cancer Res Commun ; 4(3): 706-722, 2024 03 08.
Article en En | MEDLINE | ID: mdl-38421310
ABSTRACT
Gigaxonin is an E3 ubiquitin ligase that plays a role in cytoskeletal stability. Its role in cancer is not yet clearly understood. Our previous studies of head and neck cancer had identified gigaxonin interacting with p16 for NFκB ubiquitination. To explore its role in cancer cell growth suppression, we analyzed normal and tumor DNA from cervical and head and neck cancers. There was a higher frequency of exon 8 SNP (c.1293 C>T, rs2608555) in the tumor (46% vs. 25% normal, P = 0.011) pointing to a relationship to cancer. Comparison of primary tumor with recurrence and metastasis did not reveal a statistical significance. Two cervical cancer cell lines, ME180 and HT3 harboring exon 8 SNP and showing T allele expression correlated with higher gigaxonin expression, reduced in vitro cell growth and enhanced cisplatin sensitivity in comparison with C allele expressing cancer cell lines. Loss of gigaxonin expression in ME180 cells through CRISPR-Cas9 or siRNA led to aggressive cancer cell growth including increased migration and Matrigel invasion. The in vitro cell growth phenotypes were reversed with re-expression of gigaxonin. Suppression of cell growth correlated with reduced Snail and increased e-cadherin expression. Mouse tail vein injection studies showed increased lung metastasis of cells with low gigaxonin expression and reduced metastasis with reexpression of gigaxonin. We have found an association between C allele expression and RNA instability and absence of multimeric protein formation. From our results, we conclude that gigaxonin expression is associated with suppression of epithelial-mesenchymal transition through inhibition of Snail.

SIGNIFICANCE:

Our results suggest that GAN gene exon 8 SNP T allele expression correlates with higher gigaxonin expression and suppression of aggressive cancer cell growth. There is downregulation of Snail and upregulation of e-cadherin through NFκB ubiquitination. We hypothesize that exon 8 T allele and gigaxonin expression could serve as diagnostic markers of suppression of aggressive growth of head and neck cancer.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de Cabeza y Cuello Límite: Animals / Humans Idioma: En Revista: Cancer Res Commun Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de Cabeza y Cuello Límite: Animals / Humans Idioma: En Revista: Cancer Res Commun Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos