Critical role of the Ror-family of receptor tyrosine kinases in invasion and proliferation of malignant pleural mesothelioma cells

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
Takeshi SajiYasuhiro Minami

Abstract

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with poor prognosis and closely related to exposure to asbestos. MPM is a heterogeneous tumor with three main histological subtypes, epithelioid, sarcomatoid, and biphasic types, among which sarcomatoid type shows the poorest prognosis. The Ror-family of receptor tyrosine kinases, Ror1 and Ror2, is expressed in various types of tumor cells at higher levels and affects their aggressiveness. However, it is currently unknown whether they are expressed in and involved in aggressiveness of MPM. Here, we show that Ror1 and Ror2 are expressed in clinical specimens and cell lines of MPM with different histological features. Studies using MPM cell lines indicate that expression of Ror2 is associated tightly with high invasiveness of MPM cells, whereas Ror1 can contribute to their invasion in the absence of Ror2. However, both Ror1 and Ror2 promote proliferation of MPM cells. We also show that promoted invasion and proliferation of MPM cells by Ror signaling can be mediated by the Rho-family of small GTPases, Rac1, and Cdc42. These findings elucidate the critical role of Ror signaling in promoting invasion and proliferation of MPM cells.

References

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Citations

Jan 16, 2021·Cells·Kerstin MenckAnnalen Bleckmann
Dec 7, 2019·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Noriko MiyakeNagio Takigawa
Jun 23, 2021·Journal of the American Heart Association·Nicholas W ChavkinKenneth Walsh
Jan 16, 2022·Critical Reviews in Oncology/hematology·María Victoria Castro, Pablo Lopez-Bergami

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Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.

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