Increased KIF15 Expression Predicts a Poor Prognosis in Patients with Lung Adenocarcinoma

Qiao, Yuan; Chen, Jingtao; Ma, Chao; Liu, Yingmin; Li, Peitong; Wang, Yalin; Hou, Lin; Liu, Ziling

doi:10.1159/000495155

Cited by 31 publications

(31 citation statements)

References 41 publications

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“…Up to date, over 600 members of the kinesin superfamily have been identified in addition to more than 45 members of mammals [11]. Increasing studies [8,[12][13][14][15][16] have shown that KIFs is related to the initiation and progression of breast cancer, lung cancer, and pancreatic cancer. Moreover, KIFs may be therapeutic targets for non-small cell lung cancer (NSCLC) [17].…”

Section: Introductionmentioning

confidence: 99%

KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis

Ding

et al. 2020

Cancer Cell Int

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Background: Kinesin superfamily proteins (KIFs) can transport membranous organelles and protein complexes in an ATP-dependent manner. Kinesin family member 15 (KIF15) is overexpressed in various cancers. However, the function of KIF15 in gastric cancer (GC) is still unclear. Methods: GC patients' data from The Cancer Genome Atlas (TCGA) were analyzed by bioinformatics methods. The expression of KIF15 was examined in GC and paracarcinoma tissues from 41 patients to verify the analysis results. The relationship between KIF15 expression and clinical characteristics were also observed by bioinformatics methods. Kaplan-Meier survival analysis of 122 GC patients in our hospital was performed to explore the relationship between KIF15 expression levels and GC patients' prognosis. KIF15 was downregulated in GC cell lines AGS and SGC-7901 by transfecting a lentivirus-mediated shRNA plasmid targeting KIF15. In vitro, GC cell proliferation and apoptosis were detected by MTT assay, colony formation assay, and Annexin V-APC staining. In vivo, xenograft experiments were used to verify the in vitro results. Furthermore, Human Apoptosis Antibody Array kit was used to screen possible targets of KIF15 in GC cell lines. Results: The bioinformatics results showed that KIF15 expression levels were higher in GC tissues than in normal tissues. IHC showed same results. High expression of KIF15 was statistical correlated with high age and early histologic stage. Kaplan-Meier curves indicated that high KIF15 expression predict poor prognosis in patients with GC. MTT assay and colony formation assay showed that KIF15 promote GC cell proliferation. Annexin V-APC staining found that KIF15 can inhibit GC cell apoptosis. Xenograft experiments reveal that downregulating KIF15 can inhibit GC tumor growth and promote GC apoptosis. Through detection of 43 anti-apoptotic proteins by the Human Apoptosis Antibody Array kit, it was confirmed that knocking down KIF15 can reduce seven anti-apoptotic proteins expression. Conclusions: Taken together, our study revealed a critical role for KIF15 to inhibit GC cell apoptosis and promote GC cell proliferation. KIF15 may decrease anti-apoptotic proteins expression by regulating apoptosis pathways. High expression of KIF15 predicts a poor prognosis in patients with GC. KIF15 might be a novel prognostic biomarker and a therapeutic target for GC.

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Section: Introductionmentioning

confidence: 99%

KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis

Ding

et al. 2020

Cancer Cell Int

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“…KIF15 ablation inhibits endocrine therapy-resistant breast cancer [23]. Additionally, KIF15 is high-expressed in lung cancer and involved in cancer development by regulating the cell cycle [22]. KIF15 also promotes the proliferation of pancreatic cancer via MEK-ERK pathway [21].…”

Section: Discussionmentioning

confidence: 99%

“…KIF15 seems to be a good target for cancer as it plays a key role during cell mitosis. Actually, KIF15 has also been demonstrated to be involved in the growth of various types of tumors, such as pancreatic cancer, lung cancer, and breast cancer [21][22][23]. However, the possible functions of KIF15 in HCC tumorigenesis and the relationship with prognosis are unclear.…”

Section: Introductionmentioning

confidence: 99%

KIF15 Promotes Proliferation and Growth of Hepatocellular Carcinoma

Sun

Shi

et al. 2020

Analytical Cellular Pathology

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Liver cancer is thought as the most common human malignancy worldwide, and hepatocellular carcinoma (HCC) accounts for nearly 90% liver cancer. Due to its poor early diagnosis and limited treatment, HCC has therefore become the most lethal malignant cancers in the world. Recently, molecular targeted therapies showed great promise in the treatment of HCC, and novel molecular therapeutic targets is urgently needed. KIF15 is a microtubule-dependent motor protein involved in multiple cell processes, such as cell division. Additionally, KIF15 has been reported to participate in the growth of various types of tumors; however, the relation between KIF15 and HCC is unclear. Herein, our study investigated the possible role of KIF15 on the progression of HCC and found that KIF15 has high expression in tumor samples from HCC patients. KIF15 could play a critical role in the regulation of cell proliferation of HCC, which was proved by in vitro and in vivo assays. In conclusion, this study confirmed that KIF15 could be a novel therapeutic target for the treatment of HCC.

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“…This redundancy between Kif15 and Eg5 is of interest as a potential factor in the disappointing ineffectiveness thus far of Eg5 inhibitors as cancer therapeutics (Tanenbaum et al , 2009;Rath and Kozielski, 2012;Milic et al , 2018;Dumas et al , 2019) . It is particularly notable since Kif15 overexpression results in lagging chromosomes (Malaby et al , 2019) , and is upregulated in a number of cancers (Ma et al , 2014;Wang et al , 2017;Qiao et al , 2018;Yu et al , 2019;Zhao et al , 2019;Sun et al , 2020;Terribas et al , 2020) . Under normal circumstances, however, Kif15 localizes predominantly to k-fiber microtubules.…”

Section: Introductionmentioning

confidence: 99%

“…This redundancy between Kif15 and Eg5 is of particular interest as a potential factor in the disappointing ineffectiveness thus far of Eg5 inhibitors as cancer therapeutics (Tanenbaum et al 2009;Milic et al 2018;Dumas et al 2019;Rath and Kozielski 2012) . Furthermore, Kif15 upregulation is found in a number of cancer types and can result in rapid cancer cell proliferation (Wang et al 2017;Zhao et al 2019;Yu et al 2019;Qiao et al 2018;Sun et al 2020;Terribas et al 2020;Ma et al 2014) . Under normal circumstances, however, Kif15 localizes predominantly to k-fiber microtubules.…”

Section: Introductionmentioning

confidence: 99%

K-fiber bundles in the mitotic spindle are mechanically reinforced by Kif15

Begley

Solon

Davis

et al. 2020

Preprint

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AbstractThe mitotic spindle, a self-constructed microtubule-based machine, segregates chromosomes into two eventual daughter nuclei. In mammalian cells, microtubule bundles called kinetochore-fibers (k-fibers) anchor chromosomes within the spindle. Chromosome segregation thus depends on the mechanical integrity of k-fibers. Here, we investigate the physical and molecular basis of k-fiber bundle cohesion. We sever k-fibers using laser ablation, thereby detaching them from poles and testing the contribution of pole-localized force generation to k-fiber cohesion. We then measure the physical response of the remaining kinetochore-bound segments of the k-fibers. We observe that microtubules within ablated k-fibers often, but not always, splay apart from their minus-ends. Furthermore, we find that minus-end clustering forces induced in response to ablation seem at least partially responsible for k-fiber splaying. We also investigate the role of the putative k-fiber-binding kinesin-12 Kif15. We find that pharmacological inhibition of Kif15 microtubule binding reduces k-fiber mechanical integrity. In contrast, inhibition of its motor activity but not its microtubule binding does not greatly affect splaying. Altogether, the data suggest that forces holding k-fibers together are of similar magnitude to other spindle forces, and that Kif15, acting as a microtubule crosslinker, helps fortify and repair k-fibers. This feature of Kif15 may help support robust k-fiber function and prevent chromosome segregation errors.

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Increased KIF15 Expression Predicts a Poor Prognosis in Patients with Lung Adenocarcinoma

Cited by 31 publications

References 41 publications

KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis

KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis

KIF15 Promotes Proliferation and Growth of Hepatocellular Carcinoma

K-fiber bundles in the mitotic spindle are mechanically reinforced by Kif15

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