Study on the expression of PAK4 and P54 protein in breast cancer

Bi, Yanqing; Tian, Mengzi; Le, Jinghong; Wang, Linlin; Liu, Xiaofang; Qu, Jianhua; Hao, Min

doi:10.1186/s12957-016-0913-6

Cited by 22 publications

(22 citation statements)

References 18 publications

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“…PAK4 overexpression or increased activity is associated with the development and progression of several tumor malignancies, including melanoma 36 , pancreatic cancer 37 and prostate cancer 38 . In breast cancer, PAK4 messenger RNA levels are also often overexpressed 39 , Fig. 7 | Pharmacological inhibition of PAK4 improves anti-PD-1 anti-tumor response.…”

Section: Discussionmentioning

confidence: 99%

PAK4 inhibition improves PD-1 blockade immunotherapy

et al. 2019

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Section: Discussionmentioning

confidence: 99%

PAK4 inhibition improves PD-1 blockade immunotherapy

et al. 2019

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“…Recently, two E3 ubiquitin ligases were proven to mediate NONO ubiquitination, though whether there is a deubiquitylase for NONO is still unclear. NONO is primarily distributed within the nucleus, although it is also found in the cytoplasm, and it increases gradually as breast cancer progresses . However, understanding the particular roles of NONO DNA, RNA, and protein in various cell processes in detail will require more studies in the future.…”

Section: Discussionmentioning

confidence: 99%

NONO and tumorigenesis: More than splicing

Feng

Deng

et al. 2020

J Cellular Molecular Medi

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The NONO (non-POU domain-containing octamer-binding protein) protein, also known as 54 kD nuclear RNA-and DNA-binding protein (p54nrb), belongs to the multifunctional DBHS (Drosophila behaviour/human splicing) family of proteins which can bind DNA, RNA and protein. 1 NONO has a nuclear localization signal (NLS) at its C-terminal, so it is located in the nucleus of most mammalian cells and is primarily distributed in the subnuclear domain named paraspeckles. 2 Emerging evidence strongly indicates new roles for NONO in tumorigenesis, including but not limited to regulating proliferation, apoptosis, cell migration and DNA damage repair. Here, we provide a comprehensive review of the NONO and its functions in tumorigenesis. AbstractThe non-POU domain-containing octamer-binding protein NONO/p54 nrb , which belongs to the Drosophila behaviour/human splicing (DBHS) family, is a multifunctional nuclear protein rarely functioning alone. Emerging solid evidences showed that NONO engages in almost every step of gene regulation, including but not limited to mRNA splicing, DNA unwinding, transcriptional regulation, nuclear retention of defective RNA and DNA repair. NONO is involved in many biological processes including cell proliferation, apoptosis, migration and DNA damage repair. Dysregulation of NONO has been found in many types of cancer. In this review, we summarize the current and fast-growing knowledge about the regulation of NONO, its biological function and implications in tumorigenesis and cancer progression. Overall, significant findings about the roles of NONO have been made, which might make NONO to be a new biomarker or/and a possible therapeutic target for cancers. K E Y W O R D S DBHS, NONO, splicing, tumorigenesis | 4369 FENG Et al.

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“…In most adult tissues, PAK4 expression is low. However, its overexpression has not only been associated with oncogenic transformation [29,30], but also with disease stage in breast clinical specimens [31][32][33]. We found that PAK1/4-driven CSC activity increased as the disease progressed in sequential metastatic samples taken from 2 ER+ breast cancer patients.…”

Section: Discussionmentioning

confidence: 74%

“…Data supporting a role in breast cancer include oncogenic transformation of immortalised mouse mammary epithelial cells by PAK4 overexpression and PAK4 RNAi reversing the malignant phenotype of MDAMB231 breast cancer cells [29,30]. Moreover, 3 independent studies on the expression of PAK4 in breast clinical specimens at different disease stages showed that high protein levels correlate with larger tumour size, lymph node involvement and invasive disease [31][32][33]. Furthermore, PAK4 expression associates with poor clinical outcome in tamoxifen-treated patients and was demonstrated to positively regulating ER transcriptional activity in an endocrine resistant breast cancer cell line [34].…”

Section: Introductionmentioning

confidence: 99%

PAK4 regulates stemness and progression in endocrine resistant ER-positive metastatic breast cancer

Santiago-Gómez¹,

Dragoni

NicAmhlaoibh

et al. 2019

Preprint

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Despite the effectiveness of endocrine therapies to treat estrogen receptor-positive (ER+) breast tumours, two thirds of patients will eventually relapse due to de novo or acquired resistance to these agents. Cancer Stem-like Cells (CSCs), a rare cell population within the tumour, accumulate after anti-estrogen treatments and are likely to contribute to their failure.Here we studied the role of p21-activated kinase 4 (PAK4) as a promising target to overcome endocrine resistance and disease progression in ER+ breast cancers. PAK4 predicts for resistance to tamoxifen and poor prognosis in 2 independent cohorts of ER+ tumours. We observed that PAK4 strongly correlates with CSC activity in metastatic patient-derived samples irrespective of breast cancer subtype. However, PAK4-driven mammosphereforming CSC activity increases alongside progression only in ER+ metastatic samples. PAK4 activity increases in ER+ models during acquired resistance to endocrine therapies. Targeting PAK4 with either CRT PAKi, a small molecule inhibitor of PAK4, or with specific siRNAs abrogates CSC activity/self-renewal in clinical samples and endocrine-resistant cells.Together, our findings establish that PAK4 regulates stemness during disease progression and that its inhibition reverses endocrine resistance in ER+ breast cancers. Highlights  PAK4 predicts for failure of endocrine therapies and poor prognosis  PAK4 drives stemness and progression in ER+ metastatic breast cancer  Targeting PAK4 abrogates breast CSC activity and restores sensitivity to endocrine treatments  Targeting PAK4 will improve outcome of ER+ breast cancer patients Keywords Breast cancer, endocrine resistance, PAK4, cancer stem cells List of Abbreviations that appeared in abstract Cancer Stem-like Cells (CSCs) p21-activated kinase 4 (PAK4) Estrogen Receptor (ER)

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Study on the expression of PAK4 and P54 protein in breast cancer

Cited by 22 publications

References 18 publications

PAK4 inhibition improves PD-1 blockade immunotherapy

PAK4 inhibition improves PD-1 blockade immunotherapy

NONO and tumorigenesis: More than splicing

PAK4 regulates stemness and progression in endocrine resistant ER-positive metastatic breast cancer

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