Stat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1

Morris, Edwin J.; Kawamura, Eiko; Gillespie, Jordan A.; Balgi, Aruna D.; Kannan, Nagarajan; Muller, William J.; Roberge, Michel; Dedhar, Shoukat

doi:10.1038/ncomms15289

Cited by 39 publications

(34 citation statements)

References 69 publications

(98 reference statements)

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“…White scale bar represents 5 μm. JNK1: c-Jun N-terminal kinase; siRNA: small interfering RNA; Stat3: signal transducer and activator of transcription 3 [Color figure can be viewed at wileyonlinelibrary.com]together, which result centrosome clustering and bipolar spindle in cancer cells(Morris et al, 2017). In the present study, we found that activation of Stat3 inhibited the centrosome amplification by high glucose, insulin and palmitic acid(Figures 5b,f) which clearly shows that Stat3 can negatively regulate centrosome amplification.…”

supporting

confidence: 60%

PCNA and JNK1‐Stat3 pathways respectively promotes and inhibits diabetes‐associated centrosome amplification by targeting at the ROCK1/14‐3‐3σ complex in human colon cancer HCT116 cells

Lü

Wang

et al. 2018

Journal Cellular Physiology

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We have recently reported that type 2 diabetes promotes centrosome amplification via enhancing the expression, biding, and centrosome translocation of rho‐associated coiled‐coil containing protein kinase 1 (ROCK1)/14‐3‐3σ complex in HCT116 cells. In the functional proteomic study, we further investigated the molecular pathways underlying the centrosome amplification using HCT116 cells. We found that treatment of HCT116 cells with high glucose, insulin, and palmitic acid triggered the centrosome amplification and increased the expressions of proliferating cell nuclear antigen (PCNA), nucleophosmin (NPM), and 14‐3‐3σ. Individual knockdown of PCNA, NPM, or 14‐3‐3σ inhibited the centrosome amplification. Knockdown of PCNA inhibited the treatment‐increased expression of ROCK1, whereas knockdown of ROCK1 did not affect the PCNA expression. High glucose, insulin, and palmitic acid also increased the expressions of c‐Jun N‐terminal kinase‐1 (JNK1) and signal transducer and activator of transcription 3 (Stat3), individual knockdown of which upregulated the treatment‐increased expression of 14‐3‐3σ and promoted the centrosome amplification. In contrast, overexpression of JNK1 inhibited the centrosome amplification. Knockdown of Stat3 enhanced the centrosome translocation of 14‐3‐3σ. Moreover, we showed that knockdown of JNK1 inhibited the treatment‐increased expression of Stat3. Knockdown of PCNA, JNK1, or Stat3 did not have an effect on NPM and vice versa. In conclusion, our results suggest that PCNA and JNK1‐Stat3 pathways respectively promotes and feedback inhibits the centrosome amplification by targeting at the ROCK1/14‐3‐3σ complex, and NPM serves as an independent signal for the centrosome amplification.

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supporting

confidence: 60%

PCNA and JNK1‐Stat3 pathways respectively promotes and inhibits diabetes‐associated centrosome amplification by targeting at the ROCK1/14‐3‐3σ complex in human colon cancer HCT116 cells

Lü

Wang

et al. 2018

Journal Cellular Physiology

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“…Conversely, the results of ITRAQ and western blot analyses demonstrated that STMN-knockdown attenuated STAT3 activation in GC cells. Previous studies have demonstrated that the STAT3 signaling pathway acts downstream of STMN and that activated STAT3 upregulates MMP expression (51)(52)(53)(54). STAT3, which is considered a point of convergence for numerous oncogenic signaling pathways, is constitutively activated in tumor cells and is known to promote cell proliferation and angiogenesis and serve a role in tumor avoidance of immune responses.…”

Section: Discussionmentioning

confidence: 99%

Stathmin gene silencing suppresses proliferation, migration and invasion of gastric cancer cells via AKT/sCLU and STAT3 signaling

et al. 2019

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Globally, gastric cancer is the fifth most common malignancy, with high rates of incidence and mortality. The high mortality rate and poor prognosis of gastric cancer are closely associated with its profound invasiveness, high incidence of metastasis, rapid proliferation, and high rate of recurrence. Previous studies have confirmed that stathmin (STMN) has an important role in the occurrence, development and prognosis of gastric cancer. However, the detailed mechanisms by which STMN affects these processes remain unclear. The aim of the present study was to determine how STMN promotes invasion, migration and proliferation in gastric cancer tumor cells. The results of immunohistochemistry indicated that STMN is overexpressed in stomach neoplasm tissues, and that it is associated with migration, invasion, proliferation and anti-apoptotic states of gastric cancer cells. The secretory proteins of gastric cancer cells with or without STMN knockdown were further analyzed using the isobaric tags for relative and absolute quantitation method to identify differentially expressed proteins verified by reverse transcription-quantitative polymerase chain reaction and western blot analysis. Inhibition of STMN decreases the levels of clusterin, cystatin C and matrix metalloproteinases, followed by inhibiting the protein kinase B and signal transducer and activation of transcription activation. These findings suggest that STMN could be a promising therapeutic target for gastric cancer.

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“…A transcription-independent mechanism of Stat3 has been reported through which cytoplasmic Stat3 modulates microtubule dynamics and cell migration via interaction with stathmin [8,9]. Moreover, Morris et al [10] have reported that Stat3 plays a role in the regulation of centrosome clustering in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Changes in pStat3 Are Involved in Meiotic Spindle Assembly in Mouse Oocytes

Haraguchi

Ikeda

Akagi

et al. 2020

IJMS

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The signal transducer and activator of transcription 3 (Stat3) is activated upon phosphorylation at Y705 (pStat3) and serves the dual function of signal transduction and transcription activation. Our previous study suggested that pStat3 is functional during oocyte maturation when transcription is silenced. Therefore, we speculated that pStat3 serves other functions. Immunocytochemical analysis revealed that pStat3 emerges at microtubule asters and spindle and is subsequently localized at the spindle poles along with pericentrin during mouse oocyte maturation. Both Stat3 and pStat3 proteins were detected in conditionally knocked out Stat3−/− mouse oocytes. pStat3 localization was the same in Stat3+/+ and Stat3−/− oocytes, and oocyte maturation proceeded normally, suggesting that pStat3 was still functional. Furthermore, the treatment of oocytes with the Stat3-specific inhibitors stattic and BP-1-102 or anti-pStat3 antibody led to significantly abnormal spindle assembly and chromosome mislocation in a dose-dependent manner, and pStat3 was either absent or improperly localized in these oocytes. Moreover, the development of pre-implantation stage embryos derived from inhibitor-treated oocytes was significantly hampered following in vitro fertilization. These findings indicate a novel function of pStat3 in spindle assembly.

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Stat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1

Cited by 39 publications

References 69 publications

PCNA and JNK1‐Stat3 pathways respectively promotes and inhibits diabetes‐associated centrosome amplification by targeting at the ROCK1/14‐3‐3σ complex in human colon cancer HCT116 cells

PCNA and JNK1‐Stat3 pathways respectively promotes and inhibits diabetes‐associated centrosome amplification by targeting at the ROCK1/14‐3‐3σ complex in human colon cancer HCT116 cells

Stathmin gene silencing suppresses proliferation, migration and invasion of gastric cancer cells via AKT/sCLU and STAT3 signaling

Dynamic Changes in pStat3 Are Involved in Meiotic Spindle Assembly in Mouse Oocytes

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