title: TUBB3/βIII-tubulin acts through the PTEN/AKT signaling axis to promote tumorigenesis and anoikis resistance in non-small cell lung cancer.
abstract: βIII-tubulin (encoded by TUBB3) expression is associated with therapeutic resistance and aggressive disease in non-small cell lung cancer (NSCLC), but the basis for its pathogenic influence is not understood. Functional and differential proteomics revealed that βIII-tubulin regulates expression of proteins associated with malignant growth and metastases. In particular, the adhesion-associated tumor suppressor maspin was differentially regulated by βIII-tubulin. Functionally, βIII-tubulin suppression altered cell morphology, reduced tumor spheroid outgrowth, and increased sensitivity to anoikis. Mechanistically, the PTEN/AKT signaling axis was defined as a critical pathway regulated by βIII-tubulin in NSCLC cells. βIII-Tubulin blockage in vivo reduced tumor incidence and growth. Overall, our findings revealed how βIII-tubulin influences tumor growth in NSCLC, defining new biologic functions and mechanism of action of βIII-tubulin in tumorigenesis.
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, University of New South Wales Australia, Sydney, New South Wales, Australia. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, University of New South Wales Australia, New South Wales, Australia.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: McCarroll
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, University of New South Wales Australia, Sydney, New South Wales, Australia.
authors.forename: Pei Pei
authors.initials: PP
authors.lastname: Gan
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, University of New South Wales Australia, Sydney, New South Wales, Australia.
authors.forename: Rafael B
authors.initials: RB
authors.lastname: Erlich
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, University of New South Wales Australia, Sydney, New South Wales, Australia.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Liu
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, University of New South Wales Australia, Sydney, New South Wales, Australia.
authors.forename: Tanya
authors.initials: T
authors.lastname: Dwarte
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, University of New South Wales Australia, Sydney, New South Wales, Australia. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, University of New South Wales Australia, New South Wales, Australia.
authors.forename: Sharon S
authors.initials: SS
authors.lastname: Sagnella
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, University of New South Wales Australia, Sydney, New South Wales, Australia.
authors.forename: Mia C
authors.initials: MC
authors.lastname: Akerfeldt
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, University of New South Wales Australia, Sydney, New South Wales, Australia.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, University of New South Wales Australia, Sydney, New South Wales, Australia.
authors.forename: Amelia L
authors.initials: AL
authors.lastname: Parker
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, University of New South Wales Australia, Sydney, New South Wales, Australia.
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Chang
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, University of New South Wales Australia, Sydney, New South Wales, Australia.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Shum
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, University of New South Wales Australia, Sydney, New South Wales, Australia.
authors.forename: Frances L
authors.initials: FL
authors.lastname: Byrne
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, University of New South Wales Australia, Sydney, New South Wales, Australia. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, University of New South Wales Australia, New South Wales, Australia. m.kavallaris@ccia.unsw.edu.au.
authors.forename: Maria
authors.initials: M
authors.lastname: Kavallaris
mesh_terms: D000818:Animals; D023102:Anoikis / Q000502:physiology; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015843:Serpins / Q000096:biosynthesis; D015398:Signal Transduction; D018874:Spheroids, Cellular; D014404:Tubulin / Q000378:metabolism*
chemical_list: C085344:SERPIN-B5; D015843:Serpins; C498585:TUBB3 protein, human; D014404:Tubulin; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human