4.7 Article

AKAP8L enhances the sternness and chemoresistance of gastric cancer cells by stabilizing SCD1 mRNA

Journal

CELL DEATH & DISEASE
Volume 13, Issue 12, Pages -

Publisher

SPRINGERNATURE
DOI: 10.1038/s41419-022-05502-4

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Funding

  1. Major Innovation Project of Science and Technology of Shandong Province [2019ZZZY011008]
  2. National Natural Science Foundation of China [81874118]
  3. Natural Science Foundation of Shandong Province [ZR2021LZL006, ZR2021MH108]
  4. Shandong Department of Science and Technology Plan Project [2019GSF107013]

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AKAP-8L is an upregulated gene in chemoresistant gastric cancer (GC) tissues. Higher AKAP-8L expression is associated with lower survival rate in GC patients. Overexpression of AKAP-8L enhances the stemness and chemoresistance of GC cells. SCD1 plays a critical role in mediating AKAP-8L's function in GC cell stemness and chemoresistance.
Gastric cancer (GC) remains the third leading cause of cancer-related deaths. Chemoresistance is the major determinant of GC treatment failure. To explore the molecular mechanisms of GC chemoresistance, mass spectrometry was performed to detect the genes altered in expression between chemoresistant and chemosensitive GC. PRKA kinase anchor protein 8L (AKAP-8L) was identified as one of the top upregulated genes in chemoresistant GC tissues. Moreover, the higher AKAP-8L expression was associated with the lower survival rate in GC patients. Overexpression of AKAP-8L enhanced the GC cell sternness and chemoresistance of oxaliplatin in vivo and in vitro. AKAP-8L deficiency obtained the opposite results. Mechanistically, AKAP-8L interacted with Stearoyl-CoA desaturase 1 (SCD1) mRNA and IGF2BP1 protein, and regulated SCD1 mRNA stability via 1GF2BP1-dependent manner. SCD1 played a critical role in mediating the function of AKAP-8L in GC cell sternness and chemoresistance. Clinically, AKAP-8L and SCD1 protein levels was positively associated with human GC chemoresistance. Taken together, our results demonstrated that AKAP-8L facilitates GC chemoresistance via regulating SCD1-mediated sternness of GC cells. AKAP8L may represent a novel therapeutic target to overcome GC chemoresistance.

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