HOXC13 promotes cervical cancer proliferation, invasion and Warburg effect through ß-catenin/c-Myc signaling pathway.

Cervical cancer (CC) is one of the most common malignancy and is the second leading cause of death in gynecologic malignancies worldwide. The homeobox transcription factor homeobox C13 (HOXC13) has been demonstrated to play crucial roles in various cancers. However, its function in CC remains to be addressed. In the present study, upregulation of HOXC13 expression in human CC tissues was found in The Cancer Genome Atlas (TCGA) dataset and clinical samples and was associated with tumor size, FIGO stage and lymph node metastasis. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays suggested that the expression of HOXC13 was up-regulated in CC cells. Cell Counting Kit (CCK)-8, colony formation and cell cycle analysis assays indicated that HOXC13 promoted the proliferation and cycle progression of CC cells in vitro. Of note, knockdown of HOXC13 hinders tumor growth of xenograft tumor mice in vivo. Moreover, transwell and glycolysis measurement assays demonstrated that HOXC13 enhanced the migration, invasion and glycolysis of CC cells in vitro. Further mechanism analysis suggested that HOXC13 participated in CC progression through regulation of the ß-catenin/c-Myc signaling pathway. Collectively, HOXC13 facilitated cell proliferation, migration, invasion and glycolysis through modulating ß-catenin/c-Myc signaling pathway in CC, indicating that HOXC13 may provide a promising therapeutic target for the therapy of CC.

KIFC1 promotes aerobic glycolysis in endometrial cancer cells by regulating the c-myc pathway.

Endometrial cancer (EC) is a common gynecological malignant tumor worldwide. It is imperative to study pathogenesis and therapeutic targets for improving the prognosis of EC. The present study aimed to explore the function and mechanism of kinesin family member C1 (KIFC1) in EC. EC tumor and adjacent normal tissues were collected from 68 pairs of patients. The expression of KIFC1 in tissues and EC cells was analyzed by immunohistochemistry, qRT-PCR or western blot. MTT assay was used to test the cell viability. Flow cytometry was used to determine apoptosis and the cell cycle. Glucose uptake, lactate production, ATP contents and lactate dehydrogenase (LDH) activity were evaluated by a glucose metabolism kit. The expression of HMGA1, c-myc and glycolytic genes was assessed using western blot or qRT-PCR. A mouse xenograft model was established in BALB/c mice to detect tumor growth in vivo. KIFC1 was significantly upregulated in EC tumor tissues compared to adjacent normal control tissues. The upregulated expression of KIFC1 was correlated with poor prognosis in patients. Lentiviral-mediated overexpression of KIFC1 observably enhanced cell viability and reduced the apoptotic rate of Ishikawa and HEC-1B cells. Cell cycle progression was also expedited in the KIFC1 vector group. Moreover, overexpression of KIFC1 elevated glucose uptake, lactate production, ATP contents and LDH activity. However, knockdown of KIFC1 by short hairpin RNA (shRNA) showed the reverse effect on cellular functions. In addition, the expression of c-myc, GLUT1, LDHA and HK2 was increased by the KIFC1 vector. Moreover, HMGA1 regulated the expression of c-myc and glycolytic genes. Upregulated HMGA1 could rescue the effect of KIFC1 knockdown on cellular functions and the expression of glycolytic genes. Finally, KIFC1 knockdown inhibits tumor growth in vivo. The upregulation of KIFC1 was correlated with poor prognosis in EC. KIFC1 promoted aerobic glycolysis in endometrial cancer cells by regulating the HMGA1/c-myc pathway. KIFC1 may be a potential target for the diagnosis and therapy of EC.

CDK1 promotes the phosphorylation of KIFC1 to regulate the tumorgenicity of endometrial carcinoma.

OBJECTIVE: This study aims to clarify the mechanical action of cyclin-dependent protein kinase 1 (CDK1) in the development of endometrial carcinoma (EMCA), which may be associated with the phosphorylation of kinesin family member C1 (KIFC1) and further activate the PI3K/AKT pathway. METHODS: The protein and gene expression of CDK1 in EMCA tissues and tumor cell lines were evaluated by western blot, quantitative polymerase chain reaction, and immunohistochemistry staining. Next, Cell Counting Kit-8 and colony formation assay detected cell survival and proliferation. Cell migration and invasion were measured by Transwell assay. Cell apoptosis and cell cycle were tested by flow cytometry. Immunofluorescence staining of γH2AX was used to evaluate DNA damage, respectively. Subsequently, a co-immunoprecipitation assay was used to detect the interaction between CDK1 and KIFC1. The phosphorylated protein of KIFC1 and PI3K/AKT was detected by western blot. Finally, the effect of CDK1 on the tumor formation of EMCA was evaluated in a nude mouse xenograft model. RESULTS: CDK1 was highly expressed in EMCA tumor cell lines and tissues, which contributed to cell survival, proliferation, invasion, and migration, inhibited cell apoptosis, and induced DNA damage of EMCA cells dependent on the phosphorylation of KIFC1. Moreover, the CDK1-KIFC1 axis further activated PI3K/AKT pathway. Finally, CDK1 knockdown repressed tumor formation of EMCA in vivo. CONCLUSION: We report that increased CDK1 promotes tumor progression and identified it as a potential prognostic marker and therapeutic target of EMCA.

Kinesin Family Member C1 (KIFC1) Accelerates Proliferation and Invasion of Endometrial Cancer Cells Through Modulating the PI3K/AKT Signaling Pathway.

Endometrial cancer (EC) is one of the most common cancers among women worldwide. Kinesin family member C1 (KIFC1) has been demonstrated to play crucial roles in various tumors. However, the function of KIFC1 in EC remains to be revealed. In this study, upregulation of KIFC1 expression in human EC tissues was found from analysis on data from The Cancer Genome Atlas (TCGA), and positively correlated with short survival outcome of EC patients. In addition, the mRNA and protein levels of KIFC1 were confirmed to be up-regulated in EC cells (Ishikawa, HEC-1B, HEC-1A and KLE) compared to human normal endometrial stromal cells (hESCs) by quantitative real time PCR and western blot. In vitro functional experiments showed that overexpression of KIFC1 promoted proliferation, migration and invasion of EC cells, while KIFC1 depletion showed the opposite results. Moreover, KIFC1 knockdown suppressed tumor growth in mice. Further mechanism analysis showed that KIFC1 participated in the regulation of EC progression through regulating the PI3K/AKT signaling pathway. Collectively, KIFC1 promoted proliferation and invasion through modulating PI3K/AKT signaling pathway in EC, implying that KIFC1 might provide a promising therapeutic target for the therapy of EC.