Background: Gastric cancer patients often present with distant metastasis and advanced stages. Suppressing serine/threonine-protein kinase 24 (STK24, also known as MST3) is known to promote gastric tumorigenesis. Here, we investigated the association between STK24 and the metastasis of gastric cancer.Methods: CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 technology was used for genetic knockout of STK24 at the genomic DNA level in human MKN45 and mouse M12 gastric cancer cells. To assess the effects of STK24 knockdown, western blot, cell migration, and wound healing assays were conducted in vitro. An in vivo mouse model of liver metastasis was established and tested, and bioinformatics analyses were performed.Results: The knockdown of the STK24 gene enhanced cell migration and increased liver metastasis in the mouse model of gastric cancer. STK24-silenced tumors suppressed CD4+ T cells and induced the expansion of CD11b+Ly6C+ myeloid-derived suppressor cells and F4/80+ macrophages in the spleen of the mice. In MKN45 cells, STK24 silencing resulted in downregulation of E-cadherin (CDH1, Cadherin-1, or epithelial cadherin). In 38 matched specimens of gastric adenocarcinomas and normal tissues, we examined STK24 and CDH1 expression levels via western blot; a significant positive correlation was found between the expression levels of STK24 and CDH1 (R2 = 0.5507, P = 9.72 × 10−8). Furthermore, in Oncomine database and Kaplan-Meier plotter analysis, the loss of CDH1, increase in CCL2, and upregulation of CD44 were correlated with poor prognosis in gastric cancer patients.Conclusions: Our results demonstrate that knockdown of STK24 increases cell migration and metastasis. STK24 suppression is also positively correlated with CDH1 expression in gastric cancer metastasis. Having developed an experimental metastatic model of gastric cancer in syngeneic inbred mice, we have shown that STK24 is important for immune regulation and regulates CDH1 expression during gastric metastasis.

Purpose Resistance to standard chemotherapy is a critical problem for breast cancer patients. The ATP-binding cassette (ABC) superfamily transporters actively pump out drugs and play an important role in chemoresistance. ABCB1 (ABC subfamily B, member 1, also named as multidrug resistance protein 1, MDR1) and suppressive myeloid-derived suppressor cells (MDSCs) potentially involve in chemoresistance of breast cancer. The relationship between ABCB1 and MDSC is less studied. Methods Microarray or RNA sequencing data was obtained from The Cancer Genome Atlas Breast Invasive Carcinoma in Genomic Data Commons Data Portal (GDC TCGA-BRCA) and GEO database. Expression of ABCB1 and MDSC-related genes was compared. Patient-derived xenograft (PDX) from HER2-enriced breast cancer was established to investigate the association of ABCB1 and MDSC-related genes in breast cancer. Results Expression of ABCB1 was increased in doxorubicin-selected MCF-7/ADR cells. High expression of ABCB1 mRNA was correlated with lymph node metastasis and worse overall survival of breast cancer patients. ABCB1 was positively correlated with IL6, CSF1, CSF3, or PTGS2 and negatively correlated with VEGF. PDX model from HER2-enriched stage IIA breast cancer was established. Treatment with doxorubicin or paclitaxel suppressed growth of P2 tumors and expression of ABCB1. Expression of IL6, CSF1, CSF3, PTGS2 was suppressed by paclitaxel, but not by doxorubicin. Intrasplenic MDSCs, including CD11b+Ly6G+ and CD11b+Ly6C+ cells, were higher than intratumor MDSCs in PDX-carrying nude mice. Clinically, the patient developed cancer recurrence after adjuvant chemotherapy with doxorubicin-based regimen and was well-controlled after paclitaxel-trastuzumab combined therapy.Conclusions ABCB1 is a poor predictor of breast cancer patients. Regulation of MDSC-related immune factors by ABCB1 and immune response to chemotherapeutic agents also contributes to cancer recurrence and treatment effect. PDX model is suitable to test expression of targeting genes and potential interaction with immune cells.