Centrosome amplification in cancer and cancer-associated human diseases

Zhao, Ji Zhong; Ye, Qin; Wang, Lan; Lee, Shao Chin

doi:10.1016/j.bbcan.2021.188566

Cited by 29 publications

(25 citation statements)

References 91 publications

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“…Similarly, chromium (VI) compounds enhance ROS production (Leonard et al, 2004). Elevated ROS can cause DNA damage, which in turn activates DNA damage checkpoints to cause cell cycle arrest, resulting in decoupling of the centrosome duplication cycle and the cell cycle, which is known to induce CA (Zhao et al, 2021). Indeed, our results showed that ROS signaling was involved in chromium‐induced CA.…”

Section: Discussionmentioning

confidence: 99%

“…Activated PLK4 phosphorylates and recruits STIL and SAS6 to form a cartwheel structure on the mother centriole, which forms the base for centriole duplication. PLK4 also phosphorylates and activates CP110 to regulate centriole extension and microtubule assembly (Zhao et al, 2021). Overexpression or activation of any of these proteins involved in centriole duplication can cause CA, among which PLK4 appears to be the most extensively investigated protein in the context of CA (Zhao et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Hexavalent chromium induces centrosome amplification through ROS‐ATF6‐PLK4 pathway in colon cancer cells

Bian

Guo

et al. 2022

Cell Biology International

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Centrosome amplification (CA) refers to a numerical increase in centrosomes resulting in cells with more than two centrosomes. CA has been shown to initiate tumorigenesis and increase the invasive potential of cancer cells in genetically modified experimental models. Hexavalent chromium is a recognized carcinogen that causes CA and tumorigenesis as well as promotes cancer metastasis. Thus, CA appears to be a biological link between chromium and cancer. In the present study, we investigated how chromium triggers CA. Our results showed that a subtoxic concentration of chromium-induced CA in HCT116 colon cancer cells, resulted in the production of reactive oxygen species (ROS), activated ATF6 without causing endoplasmic reticulum stress, and upregulated the protein level of PLK4. Inhibition of ROS production, ATF6 activation, or PLK4 upregulation attenuated CA. Inhibition of ROS using N-acetyl-L-cysteine (NAC) inhibited chromium-induced activation of ATF6 and upregulation of PLK4. ATF6-specific siRNA knocked down the protein level and activation of ATF6, and upregulated PLK4, with no effect on ROS production. Knockdown of PLK4 protein had no effect on chromium-induced ROS production or activation of ATF6. In conclusion, our results suggest that hexavalent chromium induces CA via the ROS-ATF6-PLK4 pathway and provides molecular targets for inhibiting chromium-mediated CA, which may be useful for the assessment of CA in chromium-promoted tumorigenesis and cancer cell metastasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hexavalent chromium induces centrosome amplification through ROS‐ATF6‐PLK4 pathway in colon cancer cells

Bian

Guo

et al. 2022

Cell Biology International

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“…The proper number of centrosomes in cells is regulated by a complex network 38,39 . PLK4 activity is required for centrosome amplification that can initiate tumorigenesis and has been considered a hallmark of cancer 40 . However, keloids are quasi‐neoplastic lesions and essentially not malignant tumors, and KFs may have normal centrosome duplication.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of PLK4 expression induces apoptosis and G0/G1‐phase cell cycle arrest in keloid fibroblasts

Huang

Liu

et al. 2022

Cell Proliferation

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Objectives: Keloids are benign fibroproliferative tumors that display many cancer-like characteristics, such as progressive uncontrolled growth, lack of spontaneous regression, and extremely high rates of recurrence. Polo-like kinase 4 (PLK4) was recently identified as a master regulator of centriole replication, and its aberrant expression is closely associated with tumorigenesis. This study aimed to investigate the expression and biological role of PLK4 in the pathogenesis of keloids. Materials and Methods:We evaluated the expression of PLK4 in keloids and adjacent normal skin tissue samples. Then, we established PLK4 knockdown and overexpression cell lines in keloid fibroblasts (KFs) and normal skin fibroblasts (NFs), respectively, to investigate the roles of PLK4 in the regulation of proliferation, migration, invasion, apoptosis, and cell cycle in KFs. Centrinone B (Cen-B), a highly selective PLK4 inhibitor, was used to inhibit PLK4 activity in KFs to evaluate the therapeutic effect on KFs.Results: We discovered that PLK4 was overexpressed in keloid dermal samples and KFs compared with adjacent normal skin samples and NFs derived from the same patients. High PLK4 expression was positively associated with the proliferation, migration, and invasion of KFs. Furthermore, knockdown of PLK4 expression or inhibition of PLK4 activity by Cen-B suppressed KF growth, induced KF apoptosis via the caspase-9/3 pathway, and induced cell cycle arrest at the G0/G1 phase in vitro.Conclusions: These findings demonstrate that PLK4 is a critical regulator of KF proliferation, migration, and invasion, and thus, Cen-B is a promising candidate drug for keloid treatment. | INTRODUCTIONKeloids are benign fibroproliferative reticular dermal tumors of unknown etiopathogenesis that can occur following any dermal injury, leading to an exophytic protuberant outgrowth that invades the adjacent normal skin beyond the original wound boundary. [1][2][3] Keloids are uniquely characterized by their aggressiveness, persistence, and progressive perilesional expansile behaviors. Due to their continued growth and lack of spontaneous regression, patients usually experience intense pain and pruritus, especially for keloid contractures located near the joints, which may lead to serious dysfunction and thus affect patients' physiological and psychological health.

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“…Phosphorylation of NPM is the very early license for the duplication of centrosomes 8 . Overduplication commonly leads to CA 7 .…”

Section: Discussionmentioning

confidence: 99%

“…We reported that diabetes‐induced CA in noncancerous and cancer cells, in vivo and in vitro, respectively, with the diabetic pathophysiological factors such as high glucose, insulin, and palmitic acid as well as advanced glycation end products as triggers, 6,7 which suggests that CA is a candidate biological link between diabetes and cancer. In our previous reports, we have described several signal transduction pathways underlying the diabetes‐associated CA, 8 which include the upregulation of the protein level of nucleophosmin (NPM) 9 …”

Section: Introductionmentioning

confidence: 99%

The binding between NPM and H2B proteins signals for the diabetes‐associated centrosome amplification

Han

Guo

et al. 2022

Cell Biochemistry & Function

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Diabetes not only increases the risk for cancer but also promotes cancer metastasis. Centrosome amplification (CA) is sufficient to initiate tumorigenesis and can enhance the invasion potential of cancer cells. We have reported that diabetes can induce CA, with diabetic pathophysiological factors as the triggers, which involves the signaling of nucleophosmin (NPM). Thus, CA can serve as a candidate biological link between diabetes and cancer. In the present study, we attempted to identify the NPM binding partners and investigated whether the binding between NPM and its partner mediated the CA. We confirmed that high glucose, insulin, and palmitic acid cancer could elicit CA in the HCT16 colon cancer cells and found that the experimental treatment increased the binding between NPM and H2B, but not between p‐NPM and H2B. The molecular docking analysis supported the fact that NPM and H2B could bind to each other through various amino acid residues. The treatment also increased the colocalization of NPM and H2B in the cytosol. Importantly, disruption of the NPM1–H2B complex by individual knockdown of the protein level of NPM or H2B led to the inhibition of the treatment‐evoked CA. In conclusion, our results suggest that the binding between NPM and H2B proteins signals for the CA by high glucose, insulin, and palmitic acid.

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Centrosome amplification in cancer and cancer-associated human diseases

Cited by 29 publications

References 91 publications

Hexavalent chromium induces centrosome amplification through ROS‐ATF6‐PLK4 pathway in colon cancer cells

Hexavalent chromium induces centrosome amplification through ROS‐ATF6‐PLK4 pathway in colon cancer cells

Downregulation of PLK4 expression induces apoptosis and G0/G1‐phase cell cycle arrest in keloid fibroblasts

The binding between NPM and H2B proteins signals for the diabetes‐associated centrosome amplification

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