Association of SYK Genetic Variations with Breast Cancer Pathogenesis

Shakeel, Shafaq; Mahjabeen, Ishrat; Kayani, Mahmood Akhtar; Faryal, Rani

doi:10.7314/apjcp.2013.14.5.3309

Cited by 12 publications

(7 citation statements)

References 17 publications

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“…Accumulating evidence revealed that SYK is also required for non-hematopoietic tumors (35–39), including colorectal, breast and hepatocellular cancer. In contrast to the possible tumor-promoting functions for SYK in hematological tumors (4), global SYK inversely inhibits tumor progression in the majority of non-hematopoietic tumors (6,8).…”

Section: Discussionmentioning

confidence: 99%

Alternative splicing of spleen tyrosine kinase differentially regulates colorectal cancer progression

Chen

et al. 2016

Oncology Letters

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Spleen tyrosine kinase (SYK) has been reported as a potential tumor suppressor in colorectal cancer (CRC). However, the role of alternative splicing of SYK in carcinogenesis remains unclear. In the present study, SYK isoforms were overexpressed in the human CRC HCT 116 cell line using lentiviral expression vectors to investigate the biological functions of full length SYK [SYK(L)] and short form SYK [SYK(S)] in CRC. Real-time cellular analysis and the 5-ethynyl-2-deoxyuridine assay were used to detect the effects of SYK(L) and SYK(S) on cell proliferation. Cell cycle progression and migration were assessed via flow cytometry and Transwell assays, respectively. The results revealed that the recombinant lentivirus with SYK(L) overexpression significantly suppressed the proliferation and metastasis of CRC cells, while SYK(S) overexpression did not. In addition, MTS assays demonstrated that SYK(L) and SYK(S) increased the cellular sensitivity to 5-fluorouracil (5-FU), suggesting that SYK(L) and 5-FU produce a significant synergistic effect on CRC cell proliferation, while SYK(S) has an effect on modulating CRC 5-FU sensitivity. Furthermore, quantitative polymerase chain reaction results revealed that SYK(L) was downregulated in 69% of 26 pairs of CRC and adjacent non-cancerous tissues, whereas SYK(S) exhibited no significant differences between tumor and normal tissues. Overall, the present data provides evidence that SYK(L) is a tumor suppressor in CRC, and both SYK(L) and SYK(S) may serve as important predictors in the chemotherapeutic treatment of CRC.

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Section: Discussionmentioning

confidence: 99%

Alternative splicing of spleen tyrosine kinase differentially regulates colorectal cancer progression

Chen

et al. 2016

Oncology Letters

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“…Estrogen and progesterone receptors (ER, PR) and HER-2/neu greatly influence the management of the malignancy (Rampaul et al, 2001) and generally has been found-be lower in Asian countries than those in the Africa, western world, USA and Australia (Ahmed et al, 2007;Hedayati-Moghadam 2008;Ahmed et al, 2011). Relation of menopausal age with breast cancer has been reported inconsistently (Schultz et al, 2005;Shakeel et al, 2013) where we cannot ignore the effects of adjuvant treatment of breast cancer on their menopausal age (Rosenberg and Partridge, 2013).…”

Section: Discussionmentioning

confidence: 99%

Germline Variations of Apurinic/Apyrimidinic Endonuclease 1 (APEX1) Detected in Female Breast Cancer Patients

Ali¹,

Mahjabeen²,

Sabir³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Apurinic/apyrimidinic endonuclease 1 (APEX1) is a multifunctional protein which plays a central role in the BER pathway. APEX1 gene being highly polymorphic in cancer patients and has been indicated to have a contributive role in Apurinic/apyrimidinic (AP) site accumulation in DNA and consequently an increased risk of cancer development. In this case-control study, all exons of the APEX1 gene and its exon/intron boundaries were amplified in 530 breast cancer patients and 395 matched healthy controls and then analyzed by single-stranded conformational polymorphism followed by sequencing. Sequence analysis revealed fourteen heterozygous mutations, seven 5'UTR, one 3´UTR, two intronic and four missense. Among identified mutations one 5'UTR (rs41561214), one 3'UTR (rs17112002) and one missense mutation

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“…Moreover, it is unknown how SYK is regulated in CF cells, both epithelial and immune cells; this is a key question that needs to be addressed. Indeed, studies on breast cancer patients have reported a significant presence of different variations of the SYK gene which are associated with breast cancer pathogenesis [38]. The role of SYK in cellular responses to P. aeruginosa in infected animal models with a CFTR deficiency is completely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have revealed the importance of SYK during fungal infection by Aspergillus fumigatus [37]. Researchers have proved that SYK associates with invasive breast cancer [38] and is closely related to the occurrence and development of digestive tract tumors [39].…”

Section: Syk and Innate Immunitymentioning

confidence: 99%

Spleen Tyrosine Kinase as a Target Therapy for <b><i>Pseudomonas aeruginosa</i></b> Infection

Alhazmi

2018

J Innate Immun

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Spleen tyrosine kinase (SYK) is a nonreceptor tyrosine kinase which associates directly with extracellular receptors, and is critically involved in signal transduction pathways in a variety of cell types for the regulation of cellular responses. SYK is expressed ubiquitously in immune and nonimmune cells, and has a much wider biological role than previously recognized. Several studies have highlighted SYK as a key player in the pathogenesis of a multitude of diseases. Pseudomonas aeruginosa is an opportunistic gram-negative pathogen, which is responsible for systemic infections in immunocompromised individuals, accounting for a major cause of severe chronic lung infection in cystic fibrosis patients and subsequently resulting in a progressive deterioration of lung function. Inhibition of SYK activity has been explored as a therapeutic option in several allergic disorders, autoimmune diseases, and hematological malignancies. This review focuses on SYK as a therapeutic target, and describes the possibility of how current knowledge could be translated for therapeutic purposes to regulate the immune response to the opportunistic pathogen P. aeruginosa.

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Association of SYK Genetic Variations with Breast Cancer Pathogenesis

Cited by 12 publications

References 17 publications

Alternative splicing of spleen tyrosine kinase differentially regulates colorectal cancer progression

Alternative splicing of spleen tyrosine kinase differentially regulates colorectal cancer progression

Germline Variations of Apurinic/Apyrimidinic Endonuclease 1 (APEX1) Detected in Female Breast Cancer Patients

Spleen Tyrosine Kinase as a Target Therapy for <b><i>Pseudomonas aeruginosa</i></b> Infection

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