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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Article
  • Peer Reviewed
Dermatology Online Journal, Volume 22, Issue 9 (2016)

BackgroundA personal history of keratinocyte carcinoma (KC) is associated with increased risk for other malignancies. To assess the role of inherited cancer predisposition we investigated if family history (FH) of skin cancer plus noncutaneous malignancy is associated with the risk of KC plus another type of cancer.

MethodsThis clinic-based case-control study of non-Hispanic Caucasians had three age- and gender-matched groups: KC plus another cancer (n=49), KC only (n=50), and cancer-free controls (n=50). Patients were interviewed to assess FH in first-degree relatives of “skin cancer” and “cancer other than skin cancer.” Controls were the referent category for the risk of 1) KC only and 2) KC plus another cancer.

ResultsWhen FH was categorized into a four-level variable and evaluated across the 3 study groups, compared to the control group a FH of skin plus noncutaneous malignancy was strongly associated with risk of KC only (OR 9.9; 95% CI 1.7-59.7) and KC plus another cancer (OR 9.8; 95% CI 1.7-57.0). The ORs for FH of skin cancer only were weaker and non-significant for both KC only (OR 4.3) and KC plus another cancer (OR 6.8). FH of noncutaneous malignancy only was null across groups.

ConclusionsThe overall pattern of associations, especially the similar associations in patients with KC only and with KC plus another cancer, reinforce the known association between a family and personal history of KC but do not support a link between FH of skin plus noncutaneous malignancy and the KC cancer-prone phenotype.

    Cover page: Family history of cancer in relation to the risk of keratinocyte carcinoma plus another type of cancer: a case-control studyCreative Commons 'BY-NC-ND' version 4.0 license
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2015)
    Weak electric fields guide cell migration, known as galvanotaxis/electrotaxis. The sensor(s) cells use to detect the fields remain elusive. Here we perform a large-scale screen using an RNAi library targeting ion transporters in human cells. We identify 18 genes that show either defective or increased galvanotaxis after knockdown. Knockdown of the KCNJ15 gene (encoding inwardly rectifying K(+) channel Kir4.2) specifically abolishes galvanotaxis, without affecting basal motility and directional migration in a monolayer scratch assay. Depletion of cytoplasmic polyamines, highly positively charged small molecules that regulate Kir4.2 function, completely inhibits galvanotaxis, whereas increase of intracellular polyamines enhances galvanotaxis in a Kir4.2-dependent manner. Expression of a polyamine-binding defective mutant of KCNJ15 significantly decreases galvanotaxis. Knockdown or inhibition of KCNJ15 prevents phosphatidylinositol 3,4,5-triphosphate (PIP3) from distributing to the leading edge. Taken together these data suggest a previously unknown two-molecule sensing mechanism in which KCNJ15/Kir4.2 couples with polyamines in sensing weak electric fields.
      Cover page: KCNJ15/Kir4.2 couples with polyamines to sense weak extracellular electric fields in galvanotaxis
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