MAP3K Family Review and Correlations with Patient Survival Outcomes in Various Cancer Types

Nguyen, Khoa; Tran, Minh N.; Rivera, Andrew; Cheng, Thomas; Windsor, Gabrielle O.; Chabot, A Bert; Cavanaugh, Jane E.; Collins‐Burow, Bridgette M.; Lee, Sean Bong; Drewry, David H.; Flaherty, Patrick; Burow, Matthew E.

doi:10.31083/j.fbl2705167

Cited by 16 publications

(7 citation statements)

References 162 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the MAPK signaling pathway is complex and the functions of the pathway cannot be generalized to a single gene and protein. MAP3K15 belongs to the large MAP3K family, including over 24 characterized proteins, which remains understudied 21 . There is a need to better understand the functional implications of MAP3K15 variants.…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis of the X chromosome in people with Lewy body dementia nominates new risk loci

Bayram,

Reho,

Litvan

et al. 2024

npj Parkinsons Dis.

View full text Add to dashboard Cite

Sex influences the prevalence and symptoms of Lewy body dementia (LBD). However, genome-wide association studies typically focus on autosomal variants and exclude sex-specific risk factors. We addressed this gap by performing an X chromosome-wide association study using whole-genome sequence data from 2591 LBD cases and 4391 controls. We identified a significant risk locus within intron 1 of MAP3K15 (rs141773145, odds ratio = 2.42, 95% confidence interval = 1.65–3.56, p-value = 7.0 × 10−6) in female LBD cases conditioned for APOE ε4 dosage. The locus includes an enhancer region that regulates MAP3K15 expression in ganglionic eminence cells derived from primary cultured neurospheres. Rare variant burden testing showed differential enrichment of missense mutations in TEX13A in female LBD cases, that did not reach significance (p-value = 1.34 × 10−4). These findings support the sex-specific effects of genetic factors and a potential role of Alzheimer’s-related risk for females with LBD.

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic analysis of the X chromosome in people with Lewy body dementia nominates new risk loci

Bayram,

Reho,

Litvan

et al. 2024

npj Parkinsons Dis.

View full text Add to dashboard Cite

show abstract

“…MAP3K1 is a tumor suppressor [31,32] and cancer driver gene [33]. MAP3K1 encodes a serine-threonine kinase in the MAP3K family which acts within the MAP-signaling pathway, triggering expression of genes important for angiogenesis, proliferation, and cell migration.…”

Section: Discussionmentioning

confidence: 99%

“…MAP3K1 encodes a serine-threonine kinase in the MAP3K family which acts within the MAP-signaling pathway, triggering expression of genes important for angiogenesis, proliferation, and cell migration. MAP3K1 is frequently mutated in human cancers, and mutations of this gene are the second-most prevalent genetic variation in BC [31]. Somatic mutations of MAP3K1 are observed in 6% of BC cases, predominantly in ER-positive BC [34].…”

Section: Discussionmentioning

confidence: 99%

Association of Germline Variation in Driver Genes with Breast Cancer Risk in Chilean Population

Morales-Pison,

Tapia,

Morales-González

et al. 2023

IJMS

View full text Add to dashboard Cite

Cancer is a genomic disease, with driver mutations contributing to tumorigenesis. These potentially heritable variants influence risk and underlie familial breast cancer (BC). This study evaluated associations between BC risk and 13 SNPs in driver genes MAP3K1, SF3B1, SMAD4, ARID2, ATR, KMT2C, MAP3K13, NCOR1, and TBX3, in BRCA1/2-negative Chilean families. SNPs were genotyped using TaqMan Assay in 492 cases and 1285 controls. There were no associations between rs75704921:C>T (ARID2); rs2229032:A>C (ATR); rs3735156:C>G (KMT2C); rs2276738:G>C, rs2293906:C>T, rs4075943T:>A, rs13091808:C>T (MAP3K13); rs178831:G>A (NCOR1); or rs3759173:C>A (TBX3) and risk. The MAP3K1 rs832583 A allele (C/A+A/A) showed a protective effect in families with moderate BC history (OR = 0.7 [95% CI 0.5–0.9] p = 0.01). SF3B1 rs16865677-T (G/T+T/T) increased risk in sporadic early-onset BC (OR = 1.4 [95% CI 1.0–2.0] p = 0.01). SMAD4 rs3819122-C (A/C+C/C) increased risk in cases with moderate family history (OR = 2.0 [95% CI 1.3–2.9] p ≤ 0.0001) and sporadic cases diagnosed ≤50 years (OR = 1.6 [95% CI 1.1–2.2] p = 0.006). SMAD4 rs12456284:A>G increased BC risk in G-allele carriers (A/G + G/G) in cases with ≥2 BC/OC cases and early-onset cases (OR = 1.2 [95% CI 1.0–1.6] p = 0.04 and OR = 1.4 [95% CI 1.0–1.9] p = 0.03, respectively). Our study suggests that specific germline variants in driver genes MAP3K1, SF3B1, and SMAD4 contribute to BC risk in Chilean population.

show abstract

“…[ 55 ] This suggests possible clinical applications of this target in other cancer types, including bladder cancer. On the other hand, MAP3K family genes have been suggested cancer‐association factors, [ 56 , 57 , 58 ] but there is no clinical trial directly related to this target due to lack of selective MAP3K inhibitors. In addition, there are other known reversion therapeutic targets, TPT1/TCTP and SETDB1 from previous studies.…”

Section: Discussionmentioning

confidence: 99%

Normalizing Input–Output Relationships of Cancer Networks for Reversion Therapy

2023

View full text Add to dashboard Cite

Accumulated genetic alterations in cancer cells distort cellular stimulus‐response (or input–output) relationships, resulting in uncontrolled proliferation. However, the complex molecular interaction network within a cell implicates a possibility of restoring such distorted input–output relationships by rewiring the signal flow through controlling hidden molecular switches. Here, a system framework of analyzing cellular input–output relationships in consideration of various genetic alterations and identifying possible molecular switches that can normalize the distorted relationships based on Boolean network modeling and dynamics analysis is presented. Such reversion is demonstrated by the analysis of a number of cancer molecular networks together with a focused case study on bladder cancer with in vitro experiments and patient survival data analysis. The origin of reversibility from an evolutionary point of view based on the redundancy and robustness intrinsically embedded in complex molecular regulatory networks is further discussed.

show abstract

MAP3K Family Review and Correlations with Patient Survival Outcomes in Various Cancer Types

Cited by 16 publications

References 162 publications

Genetic analysis of the X chromosome in people with Lewy body dementia nominates new risk loci

Genetic analysis of the X chromosome in people with Lewy body dementia nominates new risk loci

Association of Germline Variation in Driver Genes with Breast Cancer Risk in Chilean Population

Normalizing Input–Output Relationships of Cancer Networks for Reversion Therapy

Contact Info

Product

Resources

About