Anosmin-1 involved in neuronal cell migration is hypoxia inducible and cancer regulated

Bixi Jian, Chandrasekharam N. Nagineni, Sreelatha Meleth, William Grizzle, Kirby Bland, Irshad Chaudry, Raghavan Raju

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Functional expression of KAL1 gene is critical in the migration of GnRH neurons from the olfactory placode to the hypothalamus in embryogenesis. this gene thus far has not been shown to play a functional role in any other physiological or pathological process either in the developed brain or in peripheral tissues. We show here that KAL1 gene expression is decreased in early stage and increased in later stages of cancers. Screening of colon, lung and ovarian cancer cDNA panels indicated significant decrease in KAL1 expression in comparison to corresponding uninvolved tissues. However, KAL1 expression increased with the progression of cancer from early (I and II) stages to later (III and IV) stages of the cancer. there was a direct correlation between the TGFβ and KAL1 expression in colon cancer cDNA. Using colon cancer cell lines, we showed that TGFβ induces KAL1 gene expression and secretion of anosmin-1 protein (KAL1 coded protein). We further report that hypoxia induces anosmin-1 expression; anosmin-1 protects cancer cells from apoptosis activated by hypoxia and increases cancer cell mobility. Using siRNA technique we found that KAL1 expression following hypoxia is hypoxia-inducible factor (HIF-1)α dependent. our results suggest that KAL1 gene expression plays an important role in cancer metastasis and protection from apoptosis.

Original languageEnglish (US)
Pages (from-to)3770-3776
Number of pages7
JournalCell Cycle
Issue number22
StatePublished - Nov 15 2009
Externally publishedYes


  • Anosmia
  • Anosmin
  • Apoptosis
  • Colon cancer
  • HIF-1α
  • Hypogonadism
  • Metastasis
  • Tumor

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


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