GSG2 (Haspin) promotes development and progression of bladder cancer through targeting KIF15 (Kinase-12)

Chen, Yuhao; Fu, Dian; Zhao, Hai; Cheng, Wen; Xu, Feng

doi:10.18632/aging.103005

Cited by 13 publications

(7 citation statements)

References 33 publications

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“…Many studies showed that KIF15 is high expressed in many human cancer tissues and is associated with poor cancer prognosis 30–32 . In this study, we found that the expression of KIF15 was higher in EC tissues than in normal endometrial tissues, increased KIF15 expression is associated with age, tumor grade and TNM stage positively.…”

Section: Discussionsupporting

confidence: 48%

“…22 In recent years, several studies have revealed that KIFs are associated with the occurrence and development of a number of cancers, so that mitotic kinesin has attracted widespread Many studies showed that KIF15 is high expressed in many human cancer tissues and is associated with poor cancer prognosis. [30][31][32] In this study, we found that the expression of KIF15 showed that the deficiency of KIF15 could significantly promote the apoptosis of EC cells.…”

Section: Discussionmentioning

confidence: 99%

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KIF15 knockdown inhibits the development of endometrial cancer by suppressing epithelial‐mesenchymal transition and stemness through Wnt/β‐catenin signaling

Huang

Sun

Diao

et al. 2023

Environmental Toxicology

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Endometrial cancer (EC) is one of the most common cancers among women, while the incidence of EC is rising. Many studies have found that Kinesin family member 15 (KIF15) is highly expressed in a series of cancers, but the role of KIF15 in EC is unclear. We detected the expression level of KIF15 in a microarray of EC tissues by immunohistochemical staining (IHC), and analyzed the correlation between the expression level of KIF15 and the pathological characteristics of patients. After inhibit the expression of KIF15 in EC cells with lentivirus, cell proliferation and apoptosis were detected respectively by CCK8 assay, flow cytometry and tunnel assay. Transwell assay and wound healing assay were used to examine the migration ability and invasion ability of EC cells. Spheroid formation assay was used to evaluate cell self‐renewal ability. In vivo tumor xenograft model was used for validation. The expressions of epithelial‐mesenchymal transition, cancer stem cells, and Wnt/β‐catenin signaling molecules were detected by Western blotting. The results showed that the expression of KIF15 in EC tissues was higher than that in normal endometrial tissues, while the expression level of KIF15 in EC was positively correlated with the pathological grade of the tumor. The down‐regulation of KIF15 reduced the proliferation, colony formation, invasion, migration and self‐renewal ability of EC cells, while promoted cell apoptosis. Knockdown of KIF15 inactivates the Wnt/β‐catenin signaling of EC cells, inhibitors of Wnt signaling can counteract the enhanced self‐renewal ability caused by KIF15 overexpression. Therefore, KIF15 may be a new potential target for diagnosis and treatment of EC.

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

KIF15 knockdown inhibits the development of endometrial cancer by suppressing epithelial‐mesenchymal transition and stemness through Wnt/β‐catenin signaling

Huang

Sun

Diao

et al. 2023

Environmental Toxicology

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“…Previous studies have shown that HASPIN is broadly and highly expressed in various cancers compared with the corresponding non-malignant tissues [ 10 , 11 , 26 ]. A recent study has also demonstrated that among the four breast cancer subtypes, luminal A breast cancer tissues had the lowest HASPIN expression levels, whereas basal-like breast cancer tissues exhibited the highest HASPIN expression [ 12 ].…”

Section: Resultsmentioning

confidence: 99%

Evaluation of the antiproliferative effects of the HASPIN inhibitor CHR-6494 in breast cancer cell lines

et al. 2021

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HASPIN is a serine/threonine kinase that regulates mitosis by phosphorylating histone H3 at threonine 3. The expression levels of HASPIN in various cancers are associated with tumor malignancy and poor survival, suggesting that HASPIN inhibition may suppress cancer growth. As HASPIN mRNA levels are elevated in human breast cancer tissues compared with adjacent normal tissues, we examined the growth-suppressive effects of CHR-6494, a potent HASPIN inhibitor, in breast cancer cell lines in vitro and in vivo. We found that HASPIN was expressed in breast cancer cells of all molecular subtypes, as well as in immortalized mammary epithelial cells. HASPIN expression levels appeared to be correlated with the cell growth rate but not the molecular subtype of breast cancer. CHR-6494 exhibited potent antiproliferative effects against breast cancer cell lines and immortalized mammary epithelial cells in vitro, but failed to inhibit the growth of MDA-MB-231 xenografted tumors under conditions that have significant effects in a colorectal cancer model. These results imply that CHR-6494 does have antiproliferative effects in some situations, and further drug screening efforts are anticipated to identify more potent and selective HASPIN inhibition for use as an anticancer agent in breast cancer patients.

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“…It has been found that KIF15 can promote the malignant progression of bladder cancer, breast cancer, gastric cancer and other tumors. 28–31 In addition, KIF15 promotes the progression of drug resistance in prostate cancer through the androgen receptor pathway. 32 In particular, a number of studies have reported that KIF15 regulates the malignant progression of tumor cells by activating the MEK-ERK signaling pathway in pancreatic cancer, bladder cancer and colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancer

Zhang

Liao

et al. 2022

Cancer Biology & Therapy

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The tumor recurrence and drug resistance of hepatocellular carcinoma (HCC) threatened patients a lot. The mechanism should be further explored. The information of expression status and survival were available in public databases. The Western blot and immunohistochemistry staining displayed the level of related proteins. CCK-8, colony-formation assays, transwell assay and wound healing assay were performed to illustrate the ability of tumor growth, invasion and migration. In vivo model was established to verify our cell experiments. In our study, we revealed that proteasome 26S subunit, non-ATPase 12 (PSMD12) was high expressed in HCC tissues and positive related to the survival. In vitro experiments suggested that PSMD12 knockdown attenuated tumor cell growth, invasion and migration. Moreover, PSMD12 interference blocked the activation of MEK-ERK pathway. The ERK inhibitor could alleviate the tumor-promoting effect in PSMD12-overexpression cells. In addition, kinesin family member 15 (KIF15) was also observed to be highly expressed in HCC and be harmful to the survival. The public database, the images of immunohistochemistry and the western blot illustrated that PSMD12 and KIF15 was positive correlated. KIF15 knockdown impaired tumor progression and tumor-promoting effect of PSMD12. The xenograft models supported the results of cell experiments. In conclusion, PSMD12 could activated MEK-ERK pathway via KIF15 upregulation, thereby promoting tumor progression.

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GSG2 (Haspin) promotes development and progression of bladder cancer through targeting KIF15 (Kinase-12)

Cited by 13 publications

References 33 publications

KIF15 knockdown inhibits the development of endometrial cancer by suppressing epithelial‐mesenchymal transition and stemness through Wnt/β‐catenin signaling

KIF15 knockdown inhibits the development of endometrial cancer by suppressing epithelial‐mesenchymal transition and stemness through Wnt/β‐catenin signaling

Evaluation of the antiproliferative effects of the HASPIN inhibitor CHR-6494 in breast cancer cell lines

PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancer

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