title: FAM13A is associated with non-small cell lung cancer (NSCLC) progression and controls tumor cell proliferation and survival.
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 HIF1α levels in the control region of these patients. Consistently, FAM13A RhoGAP was found to be associated with T cell effector molecules like HIF1α and Tbet and was downregulated in immunosuppressive CD4+CD25+Foxp3+CTLA4+T cells. TGFβ, 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 TGFβ levels. Finally, in experimental tumor cell migration, FAM13A was induced and TGFβ accelerated this process by inducing cell migration, HIF1α, and the FAM13A RhoGAP isoform. Furthermore, siRNA to FAM13A inhibited tumor cell proliferation and induced cell migration without affecting HIF1α. In conclusion, FAM13A is involved in tumor cell proliferation and downstream of TGFβ and HIF1α, 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.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Felix
authors.identifier: 0000-0003-3536-8078
authors.initials: F
authors.lastname: Eisenhut
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Lisanne
authors.initials: L
authors.lastname: Heim
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Trump
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Mittler
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Sopel
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Katerina
authors.initials: K
authors.lastname: Andreev
authors.affiliation: Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Fulvia
authors.initials: F
authors.lastname: Ferrazzi
authors.affiliation: Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Arif B
authors.initials: AB
authors.lastname: Ekici
authors.affiliation: Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Rieker
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Rebekka
authors.initials: R
authors.lastname: Springel
authors.affiliation: Department of Immune Modulation, Department of Dermatology, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Vera L
authors.initials: VL
authors.lastname: Assmann
authors.affiliation: Department of Immune Modulation, Department of Dermatology, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lechmann
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Koch
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Engelhardt
authors.affiliation: Department of Medicine 4, Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Christina
authors.identifier: 0000-0002-6391-0891
authors.initials: C
authors.lastname: Warnecke
authors.affiliation: Department of Thoracic Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Denis I
authors.initials: DI
authors.lastname: Trufa
authors.affiliation: Department of Thoracic Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Horia
authors.initials: H
authors.lastname: Sirbu
authors.affiliation: Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany.
authors.forename: Susetta
authors.initials: S
authors.lastname: Finotto
keywords: FAM13A; Non-Small Cell Lung Cancer (NSCLC); TGFβ1; metastasis; proliferation; regulatory T Cells