{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KRTAP5‑5 is a member of the keratin‐associated protein family that appears to perform distinct functions in different biological contexts. In mammary cancer cells, for example, KRTAP5‑5 has been shown to regulate cytoskeletal organization and, consequently, cellular motility and vascular invasion. Depletion of KRTAP5‑5 in E0771 mammary carcinoma cells leads to membrane blebbing, loss of keratin (notably keratins 14 and 18), and a switch to vimentin expression. This cytoskeletal re‐organization disrupts actin dynamics and reduces hemidesmosomal α6/β4‑integrin levels, which together impair extracellular matrix invasion and the ability of cancer cells to extravasate in both zebrafish and mouse models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In a seemingly unrelated context, studies in hair follicle biology have highlighted the role of KAP5 gene family members—including proteins analogous to KRTAP5‑5—in forming the hair cuticle. These proteins are characterized by extensive cysteine‐ and glycine‑rich repeats that facilitate crosslinking of keratin intermediate filaments during cuticle cell differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Complementary research has provided valuable context for these findings. For instance, in vitro and in vivo models have been developed to assess cancer cell vascular invasion and extravasation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", while genomic studies in colorectal cancer and investigations into host–microbe interactions in cystic fibrosis have broadened our understanding of molecular mechanisms underlying disease progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Together, these studies underscore a functional versatility for KRTAP5‑5: not only does it contribute to the structural integrity required during hair formation, but its regulatory influence on the cytoskeleton also serves as a switch that can modulate malignant progression.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "E B Berens, G M Sharif, M O Schmidt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Keratin-associated protein 5-5 controls cytoskeletal function and cancer cell vascular invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2016.234"}], "href": "https://doi.org/10.1038/onc.2016.234"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27375028"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27375028"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "B J Jenkins, B C Powell "}, {"type": "b", "children": [{"type": "t", "text": "Differential expression of genes encoding a cysteine-rich keratin family in the hair cuticle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (1994)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/1523-1747.ep12394770"}], "href": "https://doi.org/10.1111/1523-1747.ep12394770"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "7521375"}], "href": "https://pubmed.ncbi.nlm.nih.gov/7521375"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Eric B Berens, Ghada M Sharif, Anton Wellstein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Testing the Vascular Invasive Ability of Cancer Cells in Zebrafish (Danio Rerio)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Vis Exp (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3791/55007"}], "href": "https://doi.org/10.3791/55007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27842376"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27842376"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hongfei Teng, Renyuan Gao, Nan Qin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of recurrent and novel mutations by whole‑genome sequencing of colorectal tumors from the Han population in Shanghai, eastern China."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2018.9563"}], "href": "https://doi.org/10.3892/mmr.2018.9563"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30365144"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30365144"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Gargi Dayama, Sambhawa Priya, David E Niccum, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interactions between the gut microbiome and host gene regulation in cystic fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genome Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13073-020-0710-2"}], "href": "https://doi.org/10.1186/s13073-020-0710-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31992345"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31992345"}]}]}]}