Fig 2: SEC61G-associated gene enrichment analysis. (A) Gene oncology (GO)-biological processes (BP), GO-molecular functions (MF) and Kyoto encyclopedia of genes and genomes (KEGG) analysis of 1041 SEC61G positive co-expression genes in HNSCC (Head and Neck Squamous Cell Carcinoma (TCGA, Firehose Legacy)). (B) Enrichment plots derived from the gene set enrichment analysis (GSEA) related to high SEC61G expression in HPV-negative HNSCC based on TCGA-HNSC database. (C) GSEA related to high SEC61G expression in HPV-positive HNSCC based on TCGA-HNSC database.

Fig 3: SEC61G knockdown suppresses human kidney cancer cell invasion. A498 and 769-P cells were transfected with siSEC61G or NC. Effect of SEC61G knockdown on (A) A498 cell invasion and (B) 769-P cell invasion. In the two panels, data are presented as the mean ± SD of the number of cells in five randomly selected fields of view from three independent experiments (magnification, ×200). (C) Effect of SEC61G knockdown on E-cadherin, N-cadherin and ß-catenin protein expression levels in A498 cells. (D) Effect of SEC61G knockdown on E-cadherin, N-cadherin and ß-catenin protein expression levels in 769-P cells. Data are presented as the mean ± SD of three independent experiments. **P<0.01 and ***P<0.001 vs. NC. SEC61G, SEC61 translocon subunit-?; si, small interfering RNA; NC, negative control; E-cad, E-cadherin; N-cad, N-cadherin.

Fig 4: SEC61G knockdown promotes human kidney cancer cell apoptosis. A498 and 769-P cells were transfected with siSEC61G or NC. Effect of SEC61G knockdown on (A) A498 cell apoptosis and (B) 769-P cell apoptosis. (C) Effect of SEC61G knockdown on BCL-2, Bax, Cleaved caspase-3 protein expression levels in A498 cells. (D) Effect of SEC61G knockdown on BCL-2, Bax, Cleaved caspase-3 protein expression levels in 769-P cells. Data are presented as the mean ± SD of three independent experiments. ***P<0.001 vs. NC. SEC61G, SEC61 translocon subunit-?; si, small interfering RNA; NC, negative control.

Fig 5: CDK4/6 inhibitor and EGFR inhibitor increase MHC-I expression by targeting E2F1/SEC61G axis. (A) “Transcription Factor Target” analysis for 2275 co-expressed genes related to SEC61G in HNSCC (Head and Neck Squamous Cell Carcinoma (TCGA, Firehose Legacy)) through webgestalt approach. (B) The correlation between the expression of SEC61G and EGFR in HNSC normal and HNSC tumor based on TCGA-HNSC database. (C) Combination Palbociclib and Cetuximab in Patient-Derived Tumor Xenograft (PDX) model related to hypopharyngeal squamous cell carcinoma. Hypopharyngeal cancer PDX models were treated with control, Palbociclib (100 mg/kg/day), Cetuximab (1 mg/week) or Cetuximab plus Palbociclib for 28 days (n = 6 per group). The growth curves of xenografts are shown. After 28 days, the mice were killed, and tumors were dissected, weighed and photographed. One-way ANOVA and Tukey’s multiple comparisons test. *p < .05, **p < .01, ***p < .001. Pal, Palbociclib; Cet, Cetuximab; ns, not significant. (D) Immunohistochemistry staining of E2F1, SEC61G, and HLA class I ABC (MHC-I) in PDX models after treatments. Pal, Palbociclib treatment mouse; Cet, Cetuximab treatment mouse; Pal + Cet, Palbociclib plus Cetuximab treatment mouse.