HASPIN is involved in the progression of gallbladder carcinoma

Zhu, Dawei; Gu, Xing; Lin, Zhenyu; Yu, Dandan; Wang, Jing; Li, Li

doi:10.1016/j.yexcr.2020.111863

Cited by 12 publications

(8 citation statements)

References 24 publications

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“…Despite the cell cycle recovery, the G1 and S/G2 progression remained significantly lengthened in haspin deficient cells even with p21 or p53 co‐depletion, indicating the presence of other cell cycle blockade independent of the p53‐p21 activation. A thorough understanding of haspin functions and identifying cell cycle‐specific targets should help gain in‐depth mechanistic insight into its potential as a chemotherapeutic target through single or combination inhibition 28,42–44 …”

Section: Discussionmentioning

confidence: 99%

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Loss of haspin suppresses cancer cell proliferation by interfering with cell cycle progression at multiple stages

et al. 2021

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Our recent studies have shown that haspin, a protein kinase imperative for mitosis, is engaged in the interphase progression of HeLa and U2OS cancer cells. In this investigation, we employed the Fucci reporter system and time-lapse imaging to examine the impact of haspin gene silencing on cell cycle progressions at a single-cell level. We found that the loss of haspin induced multiple cell cycle defects. Specifically, the S/G2 duration was greatly prolonged by haspin gene depletion or inhibition in synchronous HeLa cells. Haspin gene depletion in asynchronous HeLa and U2OS cells led to a similarly protracted S/G2 phase, followed by mitotic cell death or postmitotic G1 arrest. In addition, haspin deficiency resulted in robust induction of the p21 CIP1/WAF1 checkpoint protein, a target of the p53 activation. Also, co-depleting haspin with either p21 or p53 could rescue U2OS cells from postmitotic G1 arrest and partially restore their proliferation.These results substantiate the haspin's capacity to regulate interphase and mitotic progression, offering a broader antiproliferative potential of haspin loss in cancer cells.

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Section: Discussionmentioning

confidence: 99%

“…A thorough understanding of haspin functions and identifying cell cycle-specific targets should help gain in-depth mechanistic insight into its potential as a chemotherapeutic target through single or combination inhibition. 28,[42][43][44]…”

Section: Effect Of P53-p21 On Different Extents In G1 Arrestmentioning

confidence: 99%

Loss of haspin suppresses cancer cell proliferation by interfering with cell cycle progression at multiple stages

et al. 2021

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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: Haspin Is Broadly Expressed In Cancer and Normal Breast Cell Linesmentioning

confidence: 98%

“…Given that HASPIN expression is restricted to proliferating cells [9], HASPIN inhibition could be a viable strategy for cancer treatment. Of note, HASPIN was found to be upregulated in a wide range of cancers, and high HASPIN expression levels in tumors have been associated with a poor patient prognosis [8,[10][11][12]. More recently, HASPIN upregulation has been reported during gallbladder carcinoma (GBC) progression, and HASPIN silencing by shRNA inhibited proliferation of GBC cells [11].…”

Section: Introductionmentioning

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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“…Following this approach and the increasing development of chemical inhibitor drugs, strategies using Haspin as anti-cancer target are arising (Amoussou et al, 2018). Moreover, the up-regulation of this kinase in some cancer cells has corroborated a central role of Haspin in cell proliferation, increasing the interest of Haspin as a potential target for cancer treatment (Zhu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Haspin participates in Aurora phosphorylation at centromeres and contributes to chromosome congression in male mouse meiosis

Berenguer

López-Jiménez

Mena

et al. 2021

Preprint

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Chromosome segregation requires that centromeres properly attach to spindle microtubules. This is an essential step towards the accuracy of cell division and therefore must be precisely regulated in both mitosis and meiosis. One of the main centromeric regulatory signaling pathways is the Haspin-H3T3ph-chromosomal passenger complex (CPC) cascade, which is responsible for the recruitment of the CPC to the centromeres. In mitosis, Haspin kinase phosphorylates H3 at threonine 3 (H3T3ph), the essential histone mark that recruits the CPC whose catalytic component is Aurora B kinase. To date, no data has yet been presented about the action of the centromeric Haspin-H3T3ph-CPC pathway in mammalian male meiosis. We have analyzed the consequences of Haspin chemical inhibition in cultured spermatocytes using LDN-192960. Our in vitro studies suggest that Haspin kinase activity is required for proper chromosome congression during both meiotic divisions and for the recruitment of phosphorylated Aurora B at meiotic centromeres. These results have been confirmed by the characterization of the meiotic phenotype of the genetic mouse model Haspin-/-, which displays similar defects. In addition, our work demonstrates that the absence of H3T3ph histone mark does not alter SGO2 localization to meiotic centromeres. These results add new and relevant information regarding the regulation of centromere function during meiosis.

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HASPIN is involved in the progression of gallbladder carcinoma

Cited by 12 publications

References 24 publications

Loss of haspin suppresses cancer cell proliferation by interfering with cell cycle progression at multiple stages

Loss of haspin suppresses cancer cell proliferation by interfering with cell cycle progression at multiple stages

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

Haspin participates in Aurora phosphorylation at centromeres and contributes to chromosome congression in male mouse meiosis

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