FAM13A is associated with non-small cell lung cancer (NSCLC) progression and controls tumor cell proliferation and survival

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Eisenhut F, Heim L, Trump S, Mittler S, Sopel N, Andreev K, Ferrazzi F, Ekici AB, Rieker R, Springel R, Assmann V, Lechmann M, Koch S, Engelhardt M, Warnecke C, Trufa D, Sirbu H, Hartmann A, Finotto S
Zeitschrift: OncoImmunology
Jahr der Veröffentlichung: 2017
Band: 6
Heftnummer: 1
Seitenbereich: e1256526
ISSN: 2162-4011
eISSN: 2162-402X


Abstract


Genome-wide association studies (GWAS) associated Family with sequence similarity 13, member A (FAM13A) with non-small cell lung cancer (NSCLC) occurrence. Here, we found increased numbers of FAM13A protein expressing cells in the tumoral region of lung tissues from a cohort of patients with NSCLC. Moreover, FAM13A inversely correlated with CTLA4 but directly correlated with HIF1? levels in the control region of these patients. Consistently, FAM13A RhoGAP was found to be associated with T cell effector molecules like HIF1? and Tbet and was downregulated in immunosuppressive CD4(+)CD25(+)Foxp3(+)CTLA4(+) T cells. TGF?, a tumor suppressor factor, as well as siRNA to FAM13A, suppressed both isoforms of FAM13A and inhibited tumor cell proliferation. RNA-Seq analysis confirmed this finding. Moreover, siRNA to FAM13A induced TGF? levels. Finally, in experimental tumor cell migration, FAM13A was induced and TGF? accelerated this process by inducing cell migration, HIF1?, and the FAM13A RhoGAP isoform. Furthermore, siRNA to FAM13A inhibited tumor cell proliferation and induced cell migration without affecting HIF1?. In conclusion, FAM13A is involved in tumor cell proliferation and downstream of TGF? and HIF1?, FAM13A RhoGAP is associated with Th1 gene expression and lung tumor cell migration. These findings identify FAM13A as key regulator of NSCLC growth and progression.



FAU-Autoren / FAU-Herausgeber

Andreev, Katerina
Professur für Experimentelle Immunologie und Immuntherapie
Assmann, Vera
Immunmodulatorische Abteilung in der Hautklinik
Eisenhut, Felix Dr. med.
Professur für Molekulare Pneumologie
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Ferrazzi, Fulvia Dr.
Humangenetisches Institut
Hartmann, Arndt Prof. Dr. med.
Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie
Koch, Sonja Dr. rer. nat.
Molekular-Pneumologische Abteilung
Lechmann, Matthias PD Dr.
Immunmodulatorische Abteilung in der Hautklinik
Sirbu, Horia Prof. Dr.
Thoraxchirurgische Abteilung in der Chirurgischen Klinik
Sopel, Nina Dr. rer. nat.
Molekular-Pneumologische Abteilung
Trufa, Denis Dr.
Thoraxchirurgische Abteilung in der Chirurgischen Klinik
Warnecke, Christina PD Dr.
Medizinische Fakultät


Zitierweisen

APA:
Eisenhut, F., Heim, L., Trump, S., Mittler, S., Sopel, N., Andreev, K.,... Finotto, S. (2017). FAM13A is associated with non-small cell lung cancer (NSCLC) progression and controls tumor cell proliferation and survival. OncoImmunology, 6(1), e1256526. https://dx.doi.org/10.1080/2162402X.2016.1256526

MLA:
Eisenhut, Felix, et al. "FAM13A is associated with non-small cell lung cancer (NSCLC) progression and controls tumor cell proliferation and survival." OncoImmunology 6.1 (2017): e1256526.

BibTeX: 

Zuletzt aktualisiert 2018-09-10 um 02:26