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RasV12; scrib−/− Tumors: A Cooperative Oncogenesis Model Fueled by Tumor/Host Interactions

PTP61F Mediates Cell Competition and Mitigates Tumorigenesis

Cell Polarity, Cell Signaling & Cancer Laboratory, Department of Biochemistry & Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
Cell Cycle & Development Laboratory, Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC 3002, Australia
Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
Peter MacCallum Department of Oncology, Department of Anatomy & Neuroscience, Department of Biochemistry, University of Melbourne, Melbourne, VIC 3010, Australia
Author to whom correspondence should be addressed.
Academic Editor: Kwang Seok Ahn
Int. J. Mol. Sci. 2021, 22(23), 12732;
Received: 29 October 2021 / Revised: 23 November 2021 / Accepted: 23 November 2021 / Published: 25 November 2021
(This article belongs to the Special Issue Basic and Translational Models of Cooperative Oncogenesis 2.0)
Tissue homeostasis via the elimination of aberrant cells is fundamental for organism survival. Cell competition is a key homeostatic mechanism, contributing to the recognition and elimination of aberrant cells, preventing their malignant progression and the development of tumors. Here, using Drosophila as a model organism, we have defined a role for protein tyrosine phosphatase 61F (PTP61F) (orthologue of mammalian PTP1B and TCPTP) in the initiation and progression of epithelial cancers. We demonstrate that a Ptp61F null mutation confers cells with a competitive advantage relative to neighbouring wild-type cells, while elevating PTP61F levels has the opposite effect. Furthermore, we show that knockdown of Ptp61F affects the survival of clones with impaired cell polarity, and that this occurs through regulation of the JAK–STAT signalling pathway. Importantly, PTP61F plays a robust non-cell-autonomous role in influencing the elimination of adjacent polarity-impaired mutant cells. Moreover, in a neoplastic RAS-driven polarity-impaired tumor model, we show that PTP61F levels determine the aggressiveness of tumors, with Ptp61F knockdown or overexpression, respectively, increasing or reducing tumor size. These effects correlate with the regulation of the RAS–MAPK and JAK–STAT signalling by PTP61F. Thus, PTP61F acts as a tumor suppressor that can function in an autonomous and non-cell-autonomous manner to ensure cellular fitness and attenuate tumorigenesis. View Full-Text
Keywords: PTP61F; RAS; JAK–STAT; cell competition; tumorigenesis PTP61F; RAS; JAK–STAT; cell competition; tumorigenesis
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MDPI and ACS Style

La Marca, J.E.; Willoughby, L.F.; Allan, K.; Portela, M.; Goh, P.K.; Tiganis, T.; Richardson, H.E. PTP61F Mediates Cell Competition and Mitigates Tumorigenesis. Int. J. Mol. Sci. 2021, 22, 12732.

AMA Style

La Marca JE, Willoughby LF, Allan K, Portela M, Goh PK, Tiganis T, Richardson HE. PTP61F Mediates Cell Competition and Mitigates Tumorigenesis. International Journal of Molecular Sciences. 2021; 22(23):12732.

Chicago/Turabian Style

La Marca, John E., Lee F. Willoughby, Kirsten Allan, Marta Portela, Pei K. Goh, Tony Tiganis, and Helena E. Richardson 2021. "PTP61F Mediates Cell Competition and Mitigates Tumorigenesis" International Journal of Molecular Sciences 22, no. 23: 12732.

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