CKS1B promotes cell proliferation and invasion by activating STAT3/PD‐L1 and phosphorylation of Akt signaling in papillary thyroid carcinoma

Abstract

Objective To investigate role of GKS1B and its relationship between STAT3/PD‐L1 and p‐Akt in papillary thyroid carcinoma (PTC). Methods Expression of GKS1B and PD‐L1 was determined in PTC cell lines. GKS1B was overexpressed or knocked down by transfection with overexpression plasmids or si‐CKS1B. STAT3 inhibitor WP1066 was used to suppress STAT3, and PD‐L1 inhibitor Pembrolizumab was used to block PD‐L1. Cell viability and invasion were evaluated by MTT and transwell assay, respectively. The expression of STAT3, p‐STAT3, Akt, and p‐Akt was measured using Western blotting. Results Both protein levels and mRNA levels of CKS1B and PD‐L1 were remarkably up‐regulated in PTC cell lines. Knockdown of CKS1B significantly inhibited cell viability and invasion of PTC cells and suppressed STAT3/PD‐L1 signaling and Akt phosphorylation, while overexpression of CKS1B led to opposite results. Inhibition of STAT3 or PD‐L1 reversed the effects of overexpressed CKS1B on PTC cells. Conclusion The overexpression of CSK1B could promote cell viability and invasion of PTC cells through activation of STAT3/PD‐L1 signaling and Akt phosphorylation.

Increased heterogeneity in expression of genes associated with cancer progression and drug resistance

“…7 (B)). Among these targets, CKS1B has been shown to promote cancer cell proliferation and invasion [ 153 ]. Another gene, S100A4 has been associated with cancer development and progression [ 154 , 155 ].…”

CKS1B promotes the growth of ovarian cancer cells by regulating the expression of PD-L1

“…In lung adenocarcinoma, CKS1B serves as a vital regulator involved in promoting the proliferation of tumors [17]. In another study, Wang et al [13] reported that the silencing of CKS1B inhibited cell growth and invasion in papillary thyroid carcinoma (PTC). In addition, these authors reported that CKS1B and PD-L1 were substantially elevated in papillary thyroid carcinoma cells, thus indicating that CKS1B is an oncogene and promotes tumorigenesis by upregulating PD-L1 [13].…”

“…Reducing CKS1B in pancreatic cancer cells has been demonstrated to markedly lower cell viability and invasion through the modulation of PD-L1 expression [12]. Moreover, in papillary thyroid carcinoma cells, CKS1B has been found to promote proliferation and invasion by activating the signal transducer and activator of transcription 3 (STAT3)/PD-L1 and phosphorylated protein kinase B (Akt) signaling pathways [13]. Although CKS1B has been researched in various cancer types, its function in ovarian cancer remains unexplored.…”

Identification of CKS1B as a prognostic indicator and a predictive marker for immunotherapy in pancreatic cancer

“…In addition, CKS1B/STAT3/PD-L1 axis has also been reported in several studies. A study by Wang et al demonstrated that CKS1B overexpression may increase PTC viability and invasiveness by altering Akt phosphorylation and STAT3/PD-L1 signaling pathways (56). Another study also showed that PD-L1 expression may be enhanced by CKS1B/ STAT3 axis, further promoting lung cancer development (57).…”