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Knockdown of TM9SF4 triggering ER stress exerts anti‐growth effect on drug‐resistant breast cancer cells
Author(s) -
Zhu Yifei,
Yao Xiaoqiang
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.804.6
Subject(s) - gene knockdown , apoptosis , cancer research , unfolded protein response , breast cancer , cancer , programmed cell death , small hairpin rna , cancer cell , drug resistance , medicine , cell growth , pharmacology , biology , biochemistry , microbiology and biotechnology
Drug‐resistance of chemotherapy is the leading cause of mortality in breast cancer patients. Understanding how drug‐resistant cancer cell survival is of great importance for the breast cancer therapy. Here, we identified a key protein, TM9SF4, namely transmembrane 9 superfamily, isoform 4, which play vital role in drug‐resistant breast cancer survival. TM9SF4 is significantly up‐regulated in Adriamycin(ADM)‐resistant breast cancer cells MCF‐7/ADM compared to its parental wildtype cell line MCF‐7/WT. Knockdown of TM9SF4 using lenti‐TM9SF4‐shRNA dramatically decreased cell viability and induced cell death of MCF‐7/ADM. Moreover, drug‐resistant xenografts derived from animal model also showed a significantly reduced growth rate after the delivery of lenti‐TM9SF4‐shRNA. The underlying mechanism may be related to the triggering of ER stress, leading to unfolded protein response, which will induce apoptosis/necrosis, causing cell death. Our study provides TM9SF4 as a promising target for the overcoming of drug‐resistance in clinical breast cancer therapy.Elevated expression of TM9SF4 in drug‐resistant MCF‐7 cellsTM9SF4 is essential for MCF‐7/ADM cell survivalEffect of TM9SF4 inhibition on the growth of MCF‐7/ADM tumor xenograftsEffect of TM9SF4 suppression on ER stress in MCF‐7/ADM and drug‐resistant human xenografts.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .