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

Eisenhut F, Heim L, Trump S, Mittler S, Sopel N, Andreev K, Ferrazzi F, Ekici AB, Rieker R, Springel R, Assmann VE, Lechmann M, Koch S, Engelhardt M, Warnecke C, Trufa D, Sirbu H, Hartmann A, Finotto S (2017)

Publication Type: Journal article

Publication year: 2017

Journal

OncoImmunology Taylor & Francis

Book Volume: 6

Pages Range: e1256526

Journal Issue: 1

DOI: 10.1080/2162402X.2016.1256526

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.

Authors with CRIS profile

Felix Eisenhut Professur für Molekulare Pneumologie Nina Sopel Department of Molecular Pneumology Katerina Andreev Professur für Experimentelle Immuntherapie Fulvia Ferrazzi Institute of Human Genetics Arif Bülent Ekici Institute of Human Genetics Vera Elisabeth Assmann Department of Immune Modulation Matthias Lechmann Department of Immune Modulation Sonja Koch Department of Molecular Pneumology Christina Warnecke Medizinische Fakultät Denis Trufa Department of Thoracic Surgery Horia Sirbu Department of Thoracic Surgery Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Susetta Neurath-Finotto Department of Molecular Pneumology

How to cite

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.

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