Deactivation of glycogen synthase kinase-3ß by heat shockinducible tumor small protein attenuates hyperthermiainduced promigratory activity in colorectal cancer cells.
Int J Oncol
; 63(2)2023 Aug.
Article
en En
| MEDLINE
| ID: mdl-37387443
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 shockinducible tumor small protein (HITS) could counteract the promigratory 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 kinase3ß (GSK3ß) phosphorylated (p) at the serine 9 (pGSK3ßS9; inactive form) in HCT 116, RKO and SW480 CRC cells. GSK3ßS9 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 semiquantitative reverse transcriptionPCR analysis, followed by increased levels of pGSK3ßS9 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 GSK3ß inhibitor ARA014418, confirming the antimigratory effect of HITS via the deactivation of GSK3ß. The present findings indicated that the deactivation of GSK3ß sufficiently offset the promigratory effect of hyperthermia via major HSPs in CRC.
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MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Hipertermia Inducida
Límite:
Humans
Idioma:
En
Año:
2023
Tipo del documento:
Article