Cheng, Kim Jun and Mohamed, Elsa Haniffah Mejia and Syafruddin, Saiful Effendi and Ibrahim, Zaridatul Aini (2023) Interleukin-1 alpha and high mobility group box-1 secretion in polyinosinic:polycytidylic-induced colorectal cancer cells occur via RIPK1-dependent mechanism and participate in tumourigenesis. Journal of Cell Communication and Signaling, 17 (1). pp. 189-208. ISSN 18739601, DOI https://doi.org/10.1007/s12079-022-00681-3.
Full text not available from this repository.Abstract
Pathogenic infections have significant roles in the pathogenesis of colorectal cancer (CRC). These infections induce the secretion of various damage-associated molecular patterns (DAMPs) including interleukin-1 alpha (IL-1 alpha) and high mobility group box-1 (HMGB1). Despite their implication in CRC pathogenesis, the mechanism(s) that modulate the secretion of IL-1 alpha and HMGB1, along with their roles in promoting CRC tumourigenesis remain poorly understood. To understand the secretory mechanism, HT-29 and SW480 cells were stimulated with infectious mimetics; polyinosinic:polycytidylic acid Poly(I:C)], lipopolysaccharide (LPS) and pro-inflammatory stimuli; tumour necrosis factor-alpha (TNF-alpha). IL-1 alpha and HMGB1 secretion levels upon stimulation were determined via ELISA. Mechanism(s) mediating IL-1 alpha and HMGB1 secretion in CRC cells were characterized using pharmacological inhibitors and CRISPR-Cas9 gene editing targeting relevant pathways. Recombinant IL-1 alpha and HMGB1 were utilized to determine their impact in modulating pro-tumourigenic properties of CRC cells. Pharmacological inhibition showed that Poly(I:C)-induced IL-1 alpha secretion was mediated through endoplasmic reticulum (ER) stress and RIPK1 signalling pathway. The secretion of HMGB1 was RIPK1-dependent but independent of ER stress. RIPK1-targeted CRC cell pools exhibited decreased cell viability upon Poly(I:C) stimulation, suggesting a potential role of RIPK1 in CRC cells survival. IL-1 alpha has both growth-promoting capabilities and stimulates the production of pro-metastatic mediators, while HMGB1 only exhibits the latter; with its redox status having influence. We demonstrated a potential role of RIPK1-dependent signalling pathway in mediating the secretion of IL-1 alpha and HMGB1 in CRC cells, which in turn enhances CRC tumorigenesis. RIPK1, IL-1 alpha and HMGB1 may serve as potential therapeutic targets to mitigate CRC progression.
| Item Type: | Article |
|---|---|
| Funders: | Universiti Malaya [Grant No: GPF006C-2019], Malaysia Toray Science Foundation [Grant No: STRG0069] |
| Uncontrolled Keywords: | Interleukin-1 alpha (IL-1 alpha); High mobility group box-1 (HMGB1); Colorectal cancer; Inflammation; Damage-associated molecular patterns (DAMPs) |
| Subjects: | R Medicine > RC Internal medicine R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 24 Nov 2024 12:34 |
| Last Modified: | 24 Nov 2024 12:34 |
| URI: | http://eprints.um.edu.my/id/eprint/39554 |
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