Kinesin family member c1 (Kifc1/hset): A potential actionable biomarker of early stage breast tumorigenesis and progression of high-risk lesions

Nikita Wright, Zhihong Gong, Rick Kittles, Rama Natarajan, Tijana Jovanovic-Talisman, Padmashree Rida, Mark Labarge, Victoria Seewaldt

Research output: Contribution to journalReview articlepeer-review

Abstract

The enigma of why some premalignant or pre-invasive breast lesions transform and progress while others do not remains poorly understood. Currently, no radiologic or molecular biomarkers exist in the clinic that can successfully risk-stratify high-risk lesions for malignant transformation or tumor progression as well as serve as a minimally cytotoxic actionable target for at-risk subpopulations. Breast carcinogenesis involves a series of key molecular deregulatory events that prompt normal cells to bypass tumor-suppressive senescence barriers. Kinesin family member C1 (KIFC1/HSET), which confers survival of cancer cells burdened with extra centrosomes, has been observed in premalignant and pre-invasive lesions, and its expression has been shown to correlate with increasing neoplastic progression. Additionally, KIFC1 has been associated with aggressive breast tumor molecular subtypes, such as basal-like and triple-negative breast cancers. However, the role of KIFC1 in malignant transformation and its potential as a predictive biomarker of neoplastic progression remain elusive. Herein, we review compelling evidence suggesting the involvement of KIFC1 in enabling pre-neoplastic cells to bypass senescence barriers necessary to become immortalized and malignant. We also discuss evidence inferring that KIFC1 levels may be higher in premalignant lesions with a greater inclination to transform and acquire aggressive tumor intrinsic subtypes. Collectively, this evidence provides a strong impetus for further investigation into KIFC1 as a potential risk-stratifying biomarker and minimally cytotoxic actionable target for high-risk patient subpopulations.

Original languageEnglish (US)
Article number1361
JournalJournal of Personalized Medicine
Volume11
Issue number12
DOIs
StatePublished - Dec 2021

Keywords

  • Basal-like
  • Breast cancer
  • Cellular senescence
  • Centrosome amplification
  • High risk
  • Human mammary epithelial cells (HMECs)
  • Kinesin family member C1 (KIFC1/HSET)
  • Neoplastic progression
  • Tumorigenesis

ASJC Scopus subject areas

  • Medicine (miscellaneous)

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