2026-10-12T11:31:33Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34053693 2026-10-02T04:38:41Z category_388 portal_316 item_type_3 month_year_10_2026

Table 1_MYH9 confers doxorubicin resistance by stabilizing GRP78 and suppressing the PERK signaling-driven apoptotic pathway in breast cancer.docx Jing Jiang (130103) Tianzi You (25161609) Ziyi Zhao (8139873) Binlei Sheng (25161612) Zhanqi Sun (23659423) Xujun Li (14049801) Oncology and Carcinogenesis not elsewhere classified ADR-resistant breast cancer endoplasmic reticulum stress GRP78 MYH9 Background<p>MYH9 is upregulated in various malignancies, but its role in breast cancer chemoresistance remains unclear. We investigated whether MYH9 regulates doxorubicin (ADR) resistance via GRP78 stabilization and PERK pathway modulation.</p>Methods<p>MYH9 expression was analyzed in breast cancer tissues and cell lines by immunohistochemistry and western blot. ADR-resistant MCF-7 and MDA-MB-231 cell lines were established. MYH9 knockdown/overexpression and GRP78 overexpression were achieved by lentiviral transduction. Protein interactions, degradation assays, PERK signaling, apoptosis, and in vivo drug responses were evaluated.</p>Results<p>MYH9 was significantly upregulated in breast cancer tissues, particularly in triple-negative breast cancer (95.2%), and further elevated in ADR-resistant cells. MYH9 overexpression enhanced ADR tolerance, while knockdown sensitized resistant cells in vitro and in vivo. Mechanistically, MYH9 directly bound GRP78 (but not CALR or GRP94), inhibiting ubiquitin-mediated proteasomal degradation. MYH9 depletion reduced GRP78 levels and activated the PERK pathway (p-eIF2α, ATF4, CHOP), promoting apoptosis via Bax/Bad upregulation and Bcl-2 downregulation. ERS induction with thapsigargin enhanced ADR sensitivity, whereas 4-PBA attenuated it. GRP78 overexpression rescued ADR resistance, confirming GRP78 dependency.</p>Conclusion<p>MYH9 confers ADR resistance in breast cancer by stabilizing GRP78 and suppressing PERK-driven apoptosis, identifying the MYH9/GRP78 axis as a potential therapeutic target for overcoming chemoresistance.</p> 2026-10-02T04:38:41Z Dataset Dataset 10.3389/fonc.2026.1923603.s001 https://figshare.com/articles/dataset/Table_1_MYH9_confers_doxorubicin_resistance_by_stabilizing_GRP78_and_suppressing_the_PERK_signaling-driven_apoptotic_pathway_in_breast_cancer_docx/34053693 CC BY 4.0