Ectopic CH60 mediates HAPLN1-induced cell survival signaling in multiple myeloma.

Debayan De Bakshi, Yu-Chia Chen, Shelly M Wuerzberger-Davis, Min Ma, Bayley J Waters, Lingjun Li, Aussie Suzuki, Shigeki Miyamoto

Life science alliance 2023 Mar

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Multiple myeloma (MM), the second most common hematological malignancy, is generally considered incurable because of the development of drug resistance. We previously reported that hyaluronan and proteoglycan link protein 1 (HAPLN1) produced by stromal cells induces activation of NF-κB, a tumor-supportive transcription factor, and promotes drug resistance in MM cells. However, the identity of the cell surface receptor that detects HAPLN1 and thereby engenders pro-tumorigenic signaling in MM cells remains unknown. Here, we performed an unbiased cell surface biotinylation assay and identified chaperonin 60 (CH60) as the direct binding partner of HAPLN1 on MM cells. Cell surface CH60 specifically interacted with TLR4 to evoke HAPLN1-induced NF-κB signaling, transcription of anti-apoptotic genes, and drug resistance in MM cells. Collectively, our findings identify a cell surface CH60-TLR4 complex as a HAPLN1 receptor and a potential molecular target to overcome drug resistance in MM cells. © 2022 De Bakshi et al.

Citation

Debayan De Bakshi, Yu-Chia Chen, Shelly M Wuerzberger-Davis, Min Ma, Bayley J Waters, Lingjun Li, Aussie Suzuki, Shigeki Miyamoto. Ectopic CH60 mediates HAPLN1-induced cell survival signaling in multiple myeloma. Life science alliance. 2023 Mar;6(3)