Deactivation of glycogen synthase kinase-3β by heat shock‑inducible tumor small protein attenuates hyperthermia‑induced pro‑migratory activity in colorectal cancer cells

  • Authors:
    • Keita Koizumi
    • Takahiro Domoto
    • Toshinari Minamoto
    • Kazuhito Satomura
    • Hideo Nakajima
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  • Published online on: June 23, 2023     https://doi.org/10.3892/ijo.2023.5540
  • Article Number: 92
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Abstract

Hyperthermia is a promising approach for improving cancer treatment in combination with chemotherapy, radiotherapy and/or immunotherapy; however, its molecular mechanisms remain unclear. Although heat shock proteins (HSPs) are involved in hyperthermia via antigen presentation and immune activation, major HSPs including HSP90 are associated with cancer progression via tumor cell migration and metastasis. The present study showed that heat shock‑inducible tumor small protein (HITS) could counteract the pro‑migratory effects of HSPs in colorectal cancer (CRC) cells, which represents a novel function. Western blotting analysis revealed that overexpression of HITS increased the protein level of glycogen synthase kinase‑3β (GSK3β) phosphorylated (p) at the serine 9 (pGSK3βS9; inactive form) in HCT 116, RKO and SW480 CRC cells. GSK3βS9 phosphorylation was reported to suppress migration in some cancer types; therefore, by using the wound healing assay, the present study revealed that HITS overexpression decreased the migration activity of CRC cells. Induction of HITS transcription was observed at 12 and 18 h after heat shock (HS) by using semi‑quantitative reverse transcription‑PCR analysis, followed by increased levels of pGSK3βS9 protein at 24 and 30 h in CRC cells in western blotting. Thus, HS induced not only HSPs to promote cell migration, but also HITS to counteract the migratory activity of these HSPs in CRC cells. HITS knockdown in CRC cells subject to HS showed increased cell migration in wound healing assay, which was decreased by the GSK3β inhibitor AR‑A014418, confirming the anti‑migratory effect of HITS via the deactivation of GSK3β. The present findings indicated that the deactivation of GSK3β sufficiently offset the pro‑migratory effect of hyperthermia via major HSPs in CRC.
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August-2023
Volume 63 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Koizumi K, Domoto T, Minamoto T, Satomura K and Nakajima H: Deactivation of glycogen synthase kinase-3β by heat shock‑inducible tumor small protein attenuates hyperthermia‑induced pro‑migratory activity in colorectal cancer cells. Int J Oncol 63: 92, 2023.
APA
Koizumi, K., Domoto, T., Minamoto, T., Satomura, K., & Nakajima, H. (2023). Deactivation of glycogen synthase kinase-3β by heat shock‑inducible tumor small protein attenuates hyperthermia‑induced pro‑migratory activity in colorectal cancer cells. International Journal of Oncology, 63, 92. https://doi.org/10.3892/ijo.2023.5540
MLA
Koizumi, K., Domoto, T., Minamoto, T., Satomura, K., Nakajima, H."Deactivation of glycogen synthase kinase-3β by heat shock‑inducible tumor small protein attenuates hyperthermia‑induced pro‑migratory activity in colorectal cancer cells". International Journal of Oncology 63.2 (2023): 92.
Chicago
Koizumi, K., Domoto, T., Minamoto, T., Satomura, K., Nakajima, H."Deactivation of glycogen synthase kinase-3β by heat shock‑inducible tumor small protein attenuates hyperthermia‑induced pro‑migratory activity in colorectal cancer cells". International Journal of Oncology 63, no. 2 (2023): 92. https://doi.org/10.3892/ijo.2023.5540